Keiko Ozato

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc Brd4 is required for recovery from antimicrotubule drug-induced mitotic arrest: preservation of acetylated chromatin
    Akira Nishiyama
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2753, USA
    Mol Biol Cell 17:814-23. 2006
  2. ncbi request reprint IRF family proteins and type I interferon induction in dendritic cells
    Prafullakumar Tailor
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Cell Res 16:134-40. 2006
  3. pmc PLZF outreach: a finger in interferon's pie
    Keiko Ozato
    Program on Genomics in Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 30:757-8. 2009
  4. pmc TRIM family proteins and their emerging roles in innate immunity
    Keiko Ozato
    Program of Genomics and Differentiation, National Institute of Child Health and Human Development, National Institutes of Health NIH, Bethesda, Maryland 20892 2753, USA
    Nat Rev Immunol 8:849-60. 2008
  5. ncbi request reprint Toll-like receptor signaling and regulation of cytokine gene expression in the immune system
    Keiko Ozato
    National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2753, USA
    Biotechniques . 2002
  6. ncbi request reprint The interferon regulatory factor family in host defense: mechanism of action
    Keiko Ozato
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Biol Chem 282:20065-9. 2007
  7. ncbi request reprint Another road to interferon: Yasuichi Nagano's journey
    Keiko Ozato
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Drive, Bethesda, MD 20892 2753, USA
    J Interferon Cytokine Res 27:349-52. 2007
  8. pmc Brd4 marks select genes on mitotic chromatin and directs postmitotic transcription
    Anup Dey
    Laboratory of Molecular Growth Regulation, Program in Genomics of Differentiation, National Institute of Child Health and Human Development and Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biol Cell 20:4899-909. 2009
  9. ncbi request reprint IFN regulatory factor-4 and -8 govern dendritic cell subset development and their functional diversity
    Tomohiko Tamura
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 174:2573-81. 2005
  10. pmc The bromodomain protein Brd4 stimulates G1 gene transcription and promotes progression to S phase
    Kazuki Mochizuki
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Drive, Bethesda, MD 20892, USA
    J Biol Chem 283:9040-8. 2008

Collaborators

Detail Information

Publications88

  1. pmc Brd4 is required for recovery from antimicrotubule drug-induced mitotic arrest: preservation of acetylated chromatin
    Akira Nishiyama
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2753, USA
    Mol Biol Cell 17:814-23. 2006
    ..Brd4 plays an integral part in a cellular response to drug-induced mitotic stress by preserving a properly acetylated chromatin status...
  2. ncbi request reprint IRF family proteins and type I interferon induction in dendritic cells
    Prafullakumar Tailor
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Cell Res 16:134-40. 2006
    ..IFN and other cytokines produced by activated DC in turn advance DC maturation and change the phenotype and function of DC. These processes are also likely to be governed by IRF family proteins...
  3. pmc PLZF outreach: a finger in interferon's pie
    Keiko Ozato
    Program on Genomics in Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 30:757-8. 2009
    ..Interferon-induced PLZF phosphorylation and histone deacetylase 1 recruitment probably mediates the repressor-to-activator conversion...
  4. pmc TRIM family proteins and their emerging roles in innate immunity
    Keiko Ozato
    Program of Genomics and Differentiation, National Institute of Child Health and Human Development, National Institutes of Health NIH, Bethesda, Maryland 20892 2753, USA
    Nat Rev Immunol 8:849-60. 2008
    ..In this Review, we describe recent data that reveal broader antiviral and antimicrobial activities of TRIM proteins and discuss their involvement in the regulation of pathogen-recognition and transcriptional pathways in host defence...
  5. ncbi request reprint Toll-like receptor signaling and regulation of cytokine gene expression in the immune system
    Keiko Ozato
    National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2753, USA
    Biotechniques . 2002
    ..1). Together, although the basic backbone is conserved throughout evolution, the TLR signaling system in mammalian species has an added complexity to accommodate a mechanism that links innate and adaptive immunity...
  6. ncbi request reprint The interferon regulatory factor family in host defense: mechanism of action
    Keiko Ozato
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Biol Chem 282:20065-9. 2007
    ..This review deals with the diverse roles of IRFs in host defense and discusses the molecular mechanisms by which they regulate target gene transcription...
  7. ncbi request reprint Another road to interferon: Yasuichi Nagano's journey
    Keiko Ozato
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Drive, Bethesda, MD 20892 2753, USA
    J Interferon Cytokine Res 27:349-52. 2007
  8. pmc Brd4 marks select genes on mitotic chromatin and directs postmitotic transcription
    Anup Dey
    Laboratory of Molecular Growth Regulation, Program in Genomics of Differentiation, National Institute of Child Health and Human Development and Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biol Cell 20:4899-909. 2009
    ..In sum, Brd4 marks M/G1 genes for transcriptional memory during mitosis, and upon exiting mitosis, this mark acts as a signal for initiating their prompt transcription in daughter cells...
  9. ncbi request reprint IFN regulatory factor-4 and -8 govern dendritic cell subset development and their functional diversity
    Tomohiko Tamura
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 174:2573-81. 2005
    ..Together, IRF-4 and IRF-8 serve as a backbone of the molecular program regulating DC subset development and their functional diversity...
  10. pmc The bromodomain protein Brd4 stimulates G1 gene transcription and promotes progression to S phase
    Kazuki Mochizuki
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Drive, Bethesda, MD 20892, USA
    J Biol Chem 283:9040-8. 2008
    ..Brd4 recruitment was low to absent at genes not affected by Brd4 shRNA. The results indicate that Brd4 stimulates G(1) gene expression by binding to multiple G(1) gene promoters in a cell cycle-dependent manner...
  11. pmc Gene disruption study reveals a nonredundant role for TRIM21/Ro52 in NF-kappaB-dependent cytokine expression in fibroblasts
    Ryusuke Yoshimi
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
    J Immunol 182:7527-38. 2009
    ....
  12. ncbi request reprint Selective recognition of acetylated histones by bromodomain proteins visualized in living cells
    Tomohiko Kanno
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell 13:33-43. 2004
    ..Thus the recognition of histone acetylation code by bromodomains is selective, is involved in transcription, and potentially conveys transcriptional memory across cell divisions...
  13. pmc The sequestosome 1/p62 attenuates cytokine gene expression in activated macrophages by inhibiting IFN regulatory factor 8 and TNF receptor-associated factor 6/NF-kappaB activity
    Ji Young Kim
    Laboratory of Molecular Growth Regulation, Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 182:2131-40. 2009
    ..Together, p62 may provide a mechanism by which to control excessive inflammatory responses after macrophage activation...
  14. ncbi request reprint Cutting edge: IFN consensus sequence binding protein/IFN regulatory factor 8 drives the development of type I IFN-producing plasmacytoid dendritic cells
    Hideki Tsujimura
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 170:1131-5. 2003
    ..ICSBP-restored DCs produced IFN-alpha and IL-12p40 in a DC subset-selective manner with the amounts comparable to those by +/+ DCs. Together, ICSBP is essential for early pDC development and final maturation of both pDCs and mDCs...
  15. ncbi request reprint ICSBP/IRF-8 inhibits mitogenic activity of p210 Bcr/Abl in differentiating myeloid progenitor cells
    Tomohiko Tamura
    Bldg 6, Rm 2A01, Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Dr MSC 2753, Bethesda, MD 20892 2753, USA
    Blood 102:4547-54. 2003
    ..These results indicate that ICSBP inhibits growth of Bcr/Abl-transformed myeloid progenitor cells by activating several genes that interfere with the c-Myc pathway...
  16. pmc Intracellular delivery of acetyl-histone peptides inhibits native bromodomain-chromatin interactions and impairs mitotic progression
    Akira Nishiyama
    Laboratory of Molecular Growth Regulation, Genomics and Differentiation Program, National Institutes of Child Health and Human Development, National Institutes of Health, Building 6, Room 2A01, 6 Center Drive, Bethesda, MD 20892 2753, United States
    FEBS Lett 582:1501-7. 2008
    ..Together, PTD-based delivery of histone tail peptides offers a novel means to study the mechanism and biological significance of bromodomain-chromatin interactions in vivo...
  17. ncbi request reprint Cutting edge: autoantigen Ro52 is an interferon inducible E3 ligase that ubiquitinates IRF-8 and enhances cytokine expression in macrophages
    Hee Jeong Kong
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Drive, Bethesda, MD 20892, USA
    J Immunol 179:26-30. 2007
    ..Together, Ro52 is an E3 ligase for IRF-8 that acts in a non-degradation pathway of ubiquitination, and contributes to the elicitation of innate immunity in macrophages...
  18. pmc WHSC1 links transcription elongation to HIRA-mediated histone H3.3 deposition
    Naoyuki Sarai
    Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    EMBO J 32:2392-406. 2013
    ..Our results reveal a previously unrecognized role of WHSC1, which links transcriptional elongation and H3.3 deposition into activated genes through two molecularly distinct pathways. ..
  19. pmc Interaction of bovine papillomavirus E2 protein with Brd4 stabilizes its association with chromatin
    Maria G McPhillips
    Laboratory of Viral Diseases, NIAID, NIH, Building 4, Room 137, 4 Center Dr, MSC 0455, Bethesda, MD 20892 0455, USA
    J Virol 79:8920-32. 2005
    ..This study demonstrates that the segregation of papillomavirus genomes is not simply due to the passive hitchhiking of the E2/genome complex with a convenient cellular chromosomal protein...
  20. pmc The small ubiquitin-like modifier-deconjugating enzyme sentrin-specific peptidase 1 switches IFN regulatory factor 8 from a repressor to an activator during macrophage activation
    Tsung Hsien Chang
    Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 189:3548-56. 2012
    ..Together, the IRF8 SUMO conjugation/deconjugation switch is part of a larger transition in SUMO modifications that takes place upon macrophage activation, serving as a mechanism to trigger innate immune responses...
  21. pmc Gamma interferon triggers interaction between ICSBP (IRF-8) and TEL, recruiting the histone deacetylase HDAC3 to the interferon-responsive element
    Takeshi Kuwata
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Cell Biol 22:7439-48. 2002
    ..By associating with two different Ets family proteins, ICSBP exerts a dual function in IFN-gamma-dependent gene regulation in an immune system-specific manner...
  22. pmc Analysis of interleukin-21-induced Prdm1 gene regulation reveals functional cooperation of STAT3 and IRF4 transcription factors
    Hyokjoon Kwon
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA
    Immunity 31:941-52. 2009
    ..These results reveal broad cooperative gene regulation by STAT3 and IRF4...
  23. ncbi request reprint ICSBP/IRF-8 retrovirus transduction rescues dendritic cell development in vitro
    Hideki Tsujimura
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health NIH, Bethesda, MD 20892, USA
    Blood 101:961-9. 2003
    ..Taken together, this study identifies ICSBP as a factor critical for both early differentiation and final maturation of DCs...
  24. ncbi request reprint Essential role for ICSBP in the in vivo development of murine CD8alpha + dendritic cells
    Julio Aliberti
    Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases NIAID, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 101:305-10. 2003
    ..Together these results demonstrate that ICSBP is critically required for the in vivo differentiation of CD8alpha(+) DCs and may also influence the functional maturation of the CD8alpha(-) subsets...
  25. ncbi request reprint Toll-like receptor 9 signaling activates NF-kappaB through IFN regulatory factor-8/IFN consensus sequence binding protein in dendritic cells
    Hideki Tsujimura
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 172:6820-7. 2004
    ..IRF-8 reintroduction fully restored CpG activation of NF-kappaB and cytokine induction in -/- DCs. Together, TLR signals that activate NF-kappaB are diverse among different TLRs, and TLR9 signaling uniquely depends on IRF-8 in DCs...
  26. ncbi request reprint The interferon regulatory factor ICSBP/IRF-8 in combination with PU.1 up-regulates expression of tumor suppressor p15(Ink4b) in murine myeloid cells
    Martina Schmidt
    Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892 4263, USA
    Blood 103:4142-9. 2004
    ....
  27. pmc BRD4 coordinates recruitment of pause release factor P-TEFb and the pausing complex NELF/DSIF to regulate transcription elongation of interferon-stimulated genes
    Mira C Patel
    Program in Genomics of Differentiation, NICHD, National Institutes of Health, Bethesda, Maryland, USA
    Mol Cell Biol 33:2497-507. 2013
    ..Analyses with a BRD4 small-molecule inhibitor showed that IFN-induced recruitment of P-TEFb and NELF/DSIF was under the control of BRD4. We suggest a model where BRD4 coordinates both positive and negative regulation of ISG elongation...
  28. pmc Bromodomain protein Brd4 binds to GTPase-activating SPA-1, modulating its activity and subcellular localization
    Andrea Farina
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2753, USA
    Mol Cell Biol 24:9059-69. 2004
    ..This work reveals a novel link between Brd4 and a GTPase-dependent mitogenic signaling pathway...
  29. pmc Inducible deposition of the histone variant H3.3 in interferon-stimulated genes
    Tomohiko Tamura
    Laboratory of Molecular Growth Regulation, Eunice Kennedy Shriver NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 284:12217-25. 2009
    ..3 knockdown cells. Results indicate that H3.3 plays a role in IFN-mediated transcription, and its deposition leaves a prolonged post-transcriptional mark in these genes...
  30. pmc Deletion of the proline-rich region of the murine metastasis susceptibility gene Brd4 promotes epithelial-to-mesenchymal transition- and stem cell-like conversion
    Jude Alsarraj
    Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Cancer Res 71:3121-31. 2011
    ..Thus our findings suggest that BRD4 may be altering the predisposition of tumors to undergo conversion to a more de-differentiated or primitive state during metastatic progression...
  31. ncbi request reprint CpG-activated Thy1.2+ dendritic cells protect against lethal Listeria monocytogenes infection
    Ken J Ishii
    Section of Retroviral Immunology, Center for Biologics Evaluation Research, Food and Drug Administration, Bethesda, MD 20892, USA
    Eur J Immunol 35:2397-405. 2005
    ..2-) or plasmacytoid DC (mPDCA+), and secrete IFN-gamma that contributes to protection. These findings suggest that a novel Thy1.2+ DC subset plays a critical role in mediating the immunoprotective activity of CpG DNA...
  32. pmc The feedback phase of type I interferon induction in dendritic cells requires interferon regulatory factor 8
    Prafullakumar Tailor
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 27:228-39. 2007
    ..Together, these data indicate that IRF8 magnifies the second phase of IFN transcription in DCs by prolonging binding of basic transcription machinery to the IFN promoters, thereby playing a role in innate immunity...
  33. pmc Modulation of the Brd4/P-TEFb interaction by the human T-lymphotropic virus type 1 tax protein
    Won Kyung Cho
    Virus Tumor Biology Section, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 41 Medlars Dr, Bldg 41, Rm B201, Bethesda, MD 20892, USA
    J Virol 81:11179-86. 2007
    ..Our results suggest the possibility that Tax may compete and functionally substitute for Brd4 in P-TEFb regulation...
  34. pmc Partner-regulated interaction of IFN regulatory factor 8 with chromatin visualized in live macrophages
    Leopoldo Laricchia-Robbio
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2753, USA
    Proc Natl Acad Sci U S A 102:14368-73. 2005
    ..1 and/or IRF1, the mobility of IRF8 was markedly reduced, producing a more stably bound component. Together, IRF8-chromatin interaction is dynamic in live macrophages and influenced by partner proteins and immunological stimuli...
  35. pmc BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain
    Ballachanda N Devaiah
    Experimental Immunology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 109:6927-32. 2012
    ..Phosphorylation of the CTD Ser2 is inhibited in vivo by a BRD4 inhibitor that blocks its binding to chromatin. Our finding that BRD4 is an RNA polymerase II CTD Ser2 kinase implicates it as a regulator of eukaryotic transcription...
  36. pmc The chromatin-remodeling BAF complex mediates cellular antiviral activities by promoter priming
    Kairong Cui
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Cell Biol 24:4476-86. 2004
    ..We propose that constitutive binding of the BAF complex is an important mechanism for the IFN-inducible promoters to respond rapidly to IFN and virus stimulation...
  37. pmc Identification of target genes and a unique cis element regulated by IRF-8 in developing macrophages
    Tomohiko Tamura
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Dr, MSC 2753, Bethesda, MD 20892 2753, USA
    Blood 106:1938-47. 2005
    ..1 Ets transcription factor bind to this element in vivo. Collectively, these data indicate that IRF-8 stimulates transcription of target genes through a novel cis element to specify macrophage differentiation...
  38. pmc The BXH2 mutation in IRF8 differentially impairs dendritic cell subset development in the mouse
    Prafullakumar Tailor
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2753, USA
    Blood 111:1942-5. 2008
    ..Together, this work indicates that IRF8-partner interactions play different roles in CD8alpha(+) DCs and pDCs, revealing a mechanistic separation that underlies development of these DC subsets...
  39. pmc The mitotic chromosome binding activity of the papillomavirus E2 protein correlates with interaction with the cellular chromosomal protein, Brd4
    Michael K Baxter
    Laboratory of Viral Diseases, NIAID, NIH, Building 4, Room 137, 4 Center Dr, MSC 0455, Bethesda, MD 20892 0455, USA
    J Virol 79:4806-18. 2005
    ....
  40. pmc Virus-like particles activate type I interferon pathways to facilitate post-exposure protection against Ebola virus infection
    Natarajan Ayithan
    Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, United States of America
    PLoS ONE 10:e0118345. 2015
    ..Together, this study indicates that VLPs afford post-exposure protection by promoting expeditious initiation of type I IFN signaling in the host. ..
  41. pmc The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis
    Anup Dey
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 100:8758-63. 2003
    ..This colocalization also required both bromodomains. These observations indicate that Brd4 specifically recognizes acetylated histone codes, and this recognition is passed onto the chromatin of newly divided cells...
  42. pmc Activation of JNK triggers release of Brd4 from mitotic chromosomes and mediates protection from drug-induced mitotic stress
    Akira Nishiyama
    Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 7:e34719. 2012
    ..In sum, activation of JNK pathway triggers release of Brd4 from chromosomes upon nocodazole treatment, which mediates a protective response designed to minimize drug-induced mitotic stress...
  43. pmc Ebola Zaire virus blocks type I interferon production by exploiting the host SUMO modification machinery
    Tsung Hsien Chang
    Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Pathog 5:e1000493. 2009
    ....
  44. pmc Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis
    Tomohiro Watanabe
    Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA
    J Clin Invest 118:545-59. 2008
    ....
  45. doi request reprint Developmental and epigenetic regulation of the human TLR3 gene
    Analia Porrás
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, Bethesda, MD 20892, United States
    Mol Immunol 46:27-36. 2008
    ..These findings reveal a new source for variability in innate immune system function and provide a model for further study of perinatal epigenetic transitions during development...
  46. pmc The transcription factor IRF8 activates integrin-mediated TGF-β signaling and promotes neuroinflammation
    Yuko Yoshida
    Program in Genomics of Differentiation, NICHD, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 40:187-98. 2014
    ..Finally, IRF8 activated microglia and exacerbated neuroinflammation. Together, this work provides mechanistic bases by which IRF8 contributes to the pathogenesis of MS...
  47. pmc Viral infection increases glucocorticoid-induced interleukin-10 production through ERK-mediated phosphorylation of the glucocorticoid receptor in dendritic cells: potential clinical implications
    Sinnie Sin Man Ng
    Unit on Molecular Hormone Action, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 8:e63587. 2013
    ..The results may further underlie in part known exacerbation of IL-10/T helper-2-related allergic disorders by stress and viral infection...
  48. pmc Interaction of histone acetylases and deacetylases in vivo
    Satoshi Yamagoe
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Cell Biol 23:1025-33. 2003
    ..This HDAC-HAT association is partly accounted for by a direct protein-protein interaction observed in vitro. The HDAC-HAT complex may play a role in establishing a dynamic equilibrium of the two enzymes in vivo...
  49. pmc Bromodomain 4 activation predicts breast cancer survival
    Nigel P S Crawford
    Laboratory of Cancer Biology and Genetics and Laboratory of Population Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 105:6380-5. 2008
    ..Taken together, these data suggest that dysregulation of Brd4-associated pathways may play an important role in breast cancer progression and underlies multiple common prognostic signatures...
  50. pmc Virus-induced differential expression of nuclear receptors and coregulators in dendritic cells: implication to interferon production
    Sinnie Sin Man Ng
    Unit on Molecular Hormone Action, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 1109, USA
    FEBS Lett 585:1331-7. 2011
    ..Thus, NRs and coregulators are integral components of DC-organizing anti-viral response wherein NOR1 and LXRα participate in regulating interferon production...
  51. pmc Proteomic survey of ubiquitin-linked nuclear proteins in interferon-stimulated macrophages
    Ji Young Kim
    Program of Genomics in Differentiation, Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland, USA
    J Interferon Cytokine Res 31:619-28. 2011
    ....
  52. ncbi request reprint Induction of an anti-inflammatory cytokine, IL-10, in dendritic cells after toll-like receptor signaling
    Ranmal Samarasinghe
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Interferon Cytokine Res 26:893-900. 2006
    ..TLR-stimulated IL-10 production may regulate DC maturation steps, thereby influencing the ensuing immune responses...
  53. ncbi request reprint The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription
    Moon Kyoo Jang
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Cell 19:523-34. 2005
    ..Together, P-TEFb alternately interacts with Brd4 and the inhibitory subunit to maintain functional equilibrium in the cell...
  54. pmc Phosphorylation of histone H3 is functionally linked to retinoic acid receptor beta promoter activation
    Bruno Lefebvre
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    EMBO Rep 3:335-40. 2002
    ..Since such post-translational modifications were not observed at several other promoters, we conclude that histone H3 phosphorylation may be a molecular signature of the activated, retinoid-controlled mRARbeta2 gene promoter...
  55. pmc Brd4 associates with mitotic chromosomes throughout early zebrafish embryogenesis
    Reiko Toyama
    Laboratory of Molecular Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA
    Dev Dyn 237:1636-44. 2008
    ..The association of Brd4 with acetylated histones may also be conserved in early embryos as we found that histones H3 and H4 are already acetylated during pre-MBT stages...
  56. ncbi request reprint Immune cell-specific amplification of interferon signaling by the IRF-4/8-PU.1 complex
    Yuka Kanno
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Muscuolskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Interferon Cytokine Res 25:770-9. 2005
    ..1complex provides secondary IFN signaling pathways unique to the immune system. Collectively, the contribution of IRF-8 and PU.1 to IFN-regulated gene expression may in part account for immune cell-specific functions of IFNs...
  57. ncbi request reprint IFN consensus sequence binding protein/IFN regulatory factor-8 guides bone marrow progenitor cells toward the macrophage lineage
    Hideki Tsujimura
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 169:1261-9. 2002
    ..Taken together, ICSBP plays a critical role in myeloid cell development by controlling lineage selection and is indispensable for IFN-gamma-dependent modulation of progenitor cell maturation...
  58. pmc Interferon regulatory factor 8 integrates T-cell receptor and cytokine-signaling pathways and drives effector differentiation of CD8 T cells
    Fumi Miyagawa
    Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 109:12123-8. 2012
    ....
  59. ncbi request reprint Mechanistic link between PKR dimerization, autophosphorylation, and eIF2alpha substrate recognition
    Madhusudan Dey
    Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cell 122:901-13. 2005
    ..We propose an ordered mechanism of PKR activation in which catalytic-domain dimerization triggers Thr446 autophosphorylation and specific eIF2alpha substrate recognition...
  60. pmc IRF8 directs stress-induced autophagy in macrophages and promotes clearance of Listeria monocytogenes
    Monica Gupta
    Program in Genomics of Differentiation, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Commun 6:6379. 2015
    ..Together these data suggest that IRF8 is a major autophagy regulator in macrophages, essential for macrophage maturation, survival and innate immune responses. ..
  61. ncbi request reprint ICSBP/IRF-8: its regulatory roles in the development of myeloid cells
    Tomohiko Tamura
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Interferon Cytokine Res 22:145-52. 2002
    ..These results illustrate the mechanism by which the loss of ICSBP leads to immunodeficiency and CML-like syndrome and suggest ICSBP's critical role in the development of myeloid cells...
  62. pmc A Mammalian bromodomain protein, brd4, interacts with replication factor C and inhibits progression to S phase
    Tetsuo Maruyama
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 2753, USA
    Mol Cell Biol 22:6509-20. 2002
    ..Taken as a whole, the present study suggests that Brd4 regulates cell cycle progression in part by interacting with RFC...
  63. pmc BRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane
    Jude Alsarraj
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 8:e80746. 2013
    ..These differential biochemical and nuclear localization properties revealed in our study provide novel insights into the opposing roles of BRD4 isoforms in metastatic breast cancer progression. ..
  64. pmc BRD4 assists elongation of both coding and enhancer RNAs by interacting with acetylated histones
    Tomohiko Kanno
    1 Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA 2 Program in Genomics of Differentiation, National Institutes of Child Health and Human Development, Bethesda, Maryland, USA
    Nat Struct Mol Biol 21:1047-57. 2014
    ..Thus, BRD4 is involved in multiple steps of the transcription hierarchy, primarily by facilitating transcript elongation both at enhancers and on gene bodies independently of P-TEFb. ..
  65. pmc Ebola virus-like particles stimulate type I interferons and proinflammatory cytokine expression through the toll-like receptor and interferon signaling pathways
    Natarajan Ayithan
    1 Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
    J Interferon Cytokine Res 34:79-89. 2014
    ..These results indicate that eVLP stimulate early innate immune responses through TLR and type I IFN signaling pathways to protect the host from EBOV infection. ..
  66. pmc Dynamic bookmarking of primary response genes by p300 and RNA polymerase II complexes
    Jung S Byun
    Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 106:19286-91. 2009
    ....
  67. pmc Chromosomal integration of retinoic acid response elements prevents cooperative transcriptional activation by retinoic acid receptor and retinoid X receptor
    Bruno Lefebvre
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Cell Biol 22:1446-59. 2002
    ....
  68. ncbi request reprint Synergistic activation of interleukin-12 p35 gene transcription by interferon regulatory factor-1 and interferon consensus sequence-binding protein
    Jianguo Liu
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    J Biol Chem 279:55609-17. 2004
    ..This study provides novel mechanistic information on how signals initiated during innate and adaptive immune responses synergize to yield greater IL-12 production and sustained cellular immunity...
  69. ncbi request reprint IRF-8/ICSBP and IRF-1 cooperatively stimulate mouse IL-12 promoter activity in macrophages
    Atsuko Masumi
    Department of Safety Research on Biologics, National Institute of Infectious Diseases, Gakuen 4 7 1, Musashimurayama shi, Tokyo, Japan
    FEBS Lett 531:348-53. 2002
    ..Together, these results indicate that ICSBP and IRF-1 cooperatively stimulate murine IL-12 transcription through a novel regulatory element in the murine promoter...
  70. ncbi request reprint Complex formation of the interferon (IFN) consensus sequence-binding protein with IRF-1 is essential for murine macrophage IFN-gamma-induced iNOS gene expression
    Huabao Xiong
    Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 278:2271-7. 2003
    ..Complex formation of ICSBP with IRF-1 is essential for iNOS expression, and interleukin-4 attenuates the physical interaction of ICSBP with IRF-1 resulting in the inhibition of INOS gene expression...
  71. ncbi request reprint Interferon regulatory factor-2 regulates cell growth through its acetylation
    Atsuko Masumi
    Department of Safety Research on Biologics, National Institute of Infectious Diseases, Tokyo, Japan
    J Biol Chem 278:25401-7. 2003
    ..These results indicate that IRF-2 is acetylated in a cell growth-dependent manner, which enables it to contribute to transcription of cell growth-regulated promoters...
  72. ncbi request reprint Nramp1-mediated innate resistance to intraphagosomal pathogens is regulated by IRF-8, PU.1, and Miz-1
    Michal Alter-Koltunoff
    Department of Food Engineering and Biotechnology, Technion, Haifa 32000, Israel
    J Biol Chem 278:44025-32. 2003
    ..Thus, our results explain in molecular terms the role of IRF-8 in conferring innate resistance to intracellular pathogens and point to its possible involvement in autoimmune diseases...
  73. ncbi request reprint Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes
    Jianxin You
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 117:349-60. 2004
    ..The interaction of E2 with Brd4 is required to ensure the tethering of viral genomes to the host mitotic chromosomes for persistence of viral episomes in PV-infected cells...
  74. ncbi request reprint Innate immunity to intraphagosomal pathogens is mediated by interferon regulatory factor 8 (IRF-8) that stimulates the expression of macrophage-specific Nramp1 through antagonizing repression by c-Myc
    Michal Alter-Koltunoff
    Department of Biotechnology and Food Engineering, Technion Israel Institute of Technology, Haifa 32000, Israel
    J Biol Chem 283:2724-33. 2008
    ..Thus, interplay between repression and activation state of the Nramp1 promoter mediated by IRF-8 provides the molecular basis by which macrophages resist intraphagosomal pathogens at early stage after infection...
  75. ncbi request reprint Ubiquitin-dependent degradation of interferon regulatory factor-8 mediated by Cbl down-regulates interleukin-12 expression
    Huabao Xiong
    Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 280:23531-9. 2005
    ..Taken together, these results suggest that the proteasomal degradation of IRF-8 mediated by the ubiquitin E3 ligase Cbl down-regulates IL-12 expression...
  76. ncbi request reprint The role of IFN regulatory factor-3 in the cytotoxic activity of NS-9, a polyinosinic-polycytidylic acid/cationic liposome complex, against tumor cells
    Tomonori Uno
    Discovery Research Laboratories, Nippon Shinyaku Co, Ltd, 14 Nishinosho Monguchi cho, Kisshoin, Minami, Kyoto 601 8550, Japan
    Mol Cancer Ther 4:799-805. 2005
    ..We conclude that IRF3 plays a crucial role in the cytotoxic activity of NS-9 against tumor cells, whereas RNA-dependent protein kinase, RNase L, or type I IFNs are not important for its activity...
  77. ncbi request reprint IRF-8/interferon (IFN) consensus sequence-binding protein is involved in Toll-like receptor (TLR) signaling and contributes to the cross-talk between TLR and IFN-gamma signaling pathways
    Jie Zhao
    Immunobiology Center, Mount Sinai School of Medicine, 1 Gustave L Levy Place, New York, NY 10029, USA
    J Biol Chem 281:10073-80. 2006
    ..Taken together, the results suggest that the interaction of IRF-8 with TRAF6 modulates TLR signaling and may contribute to the cross-talk between IFN-gamma and TLR signal pathways...
  78. ncbi request reprint Crystal structure of the human BRD2 bromodomain: insights into dimerization and recognition of acetylated histone H4
    Yoshihiro Nakamura
    RIKEN Genomic Sciences Center, 1 7 22 Suehiro cho, Tsurumi, Yokohama 230 0045, Japan
    J Biol Chem 282:4193-201. 2007
    ..The two acetyllysine-binding pockets and a negatively charged secondary binding pocket, produced at the dimer interface in BRD2 BD1, may be the unique features that allow BRD2 BD1 to selectively bind to the acetylated H4 tail...
  79. ncbi request reprint Interferon regulatory factor-8 is indispensable for the expression of promyelocytic leukemia and the formation of nuclear bodies in myeloid cells
    Natalie Dror
    Department of Biotechnology and Food Engineering, Technion Israel Institute of Technology, Haifa 32000, Israel
    J Biol Chem 282:5633-40. 2007
    ..When IRF-8 levels are compromised, the reduced PML expression may lead to genome instability and eventually to the leukemic phenotype...
  80. ncbi request reprint Histone acetylation and subcellular localization of chromosomal protein BRD4 during mouse oocyte meiosis and mitosis
    Takashi Nagashima
    Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
    Mol Hum Reprod 13:141-8. 2007
    ....
  81. ncbi request reprint Natural killer dendritic cells are an intermediate of developing dendritic cells
    Li Chen
    Department of Pathology, Ohio State University Medical Center, 129 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA
    J Leukoc Biol 81:1422-33. 2007
    ..1(+)MHC II(-) and possess strong cytotoxic function yet show a poor ability to present antigen in the steady state. These findings suggest that NKDCs may play a critical role in linking innate and adaptive immunity...
  82. pmc Virus infection triggers SUMOylation of IRF3 and IRF7, leading to the negative regulation of type I interferon gene expression
    Toru Kubota
    Department of Virology III, National Institute of Infectious Diseases, Gakuen 4 7 1, Musashi Murayama, Tokyo, Japan
    J Biol Chem 283:25660-70. 2008
    ..Together, SUMO modification is an integral part of IRF3 and IRF7 activity that contributes to postactivation attenuation of IFN production...
  83. pmc Global nature of dynamic protein-chromatin interactions in vivo: three-dimensional genome scanning and dynamic interaction networks of chromatin proteins
    Robert D Phair
    BioInformatics Services, Rockville, MD 20854, USA
    Mol Cell Biol 24:6393-402. 2004
    ..We suggest that these properties are crucial for generating high plasticity in genome expression...
  84. pmc The alternative Ctf18-Dcc1-Ctf8-replication factor C complex required for sister chromatid cohesion loads proliferating cell nuclear antigen onto DNA
    Vladimir P Bermudez
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 100:10237-42. 2003
    ..These results support a model in which sister chromatid cohesion is linked to DNA replication...
  85. ncbi request reprint Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4
    Zhiyuan Yang
    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA
    Mol Cell 19:535-45. 2005
    ..Brd4, HEXIM1, and 7SK are all implicated in regulating cell growth, which may result from their dynamic control of the general transcription factor P-TEFb...
  86. ncbi request reprint Identification of IRF-8 and IRF-1 target genes in activated macrophages
    Natalie Dror
    Department of Biotechnology and Food Engineering, Technion Israel Institute of Technology, Haifa, Israel
    Mol Immunol 44:338-46. 2007
    ..We therefore suggest a broader role for IRF-1 and IRF-8 in macrophages differentiation and maturation, being important inflammatory mediators...
  87. ncbi request reprint Repression of IFN regulatory factor 8 by DNA methylation is a molecular determinant of apoptotic resistance and metastatic phenotype in metastatic tumor cells
    Dafeng Yang
    Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia, USA
    Cancer Res 67:3301-9. 2007
    ....
  88. ncbi request reprint The role of the interferon regulatory factor (IRF) family in dendritic cell development and function
    Lucia Gabriele
    Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Roma, Italy
    Cytokine Growth Factor Rev 18:503-10. 2007
    ....