Research Topics
| STEPHEN SMALESummaryAffiliation: University of California Country: USA Publications
Research Grants
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Detail Information
Publications
Chromatin structure and gene regulation in the immune systemStephen T Smale
Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095 1662, USA
Annu Rev Immunol 20:427-62. 2002..Finally, basic principles of gene silencing are discussed...
Dimer-specific regulatory mechanisms within the NF-κB family of transcription factorsStephen T Smale
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Immunol Rev 246:193-204. 2012..Despite significant advances, our knowledge remains limited and many years of additional work will be needed to fully understand how the dimer-specific functions of NF-κB contribute to transcriptional selectivity...
Transcriptional regulation in the innate immune systemStephen T Smale
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Curr Opin Immunol 24:51-7. 2012....- Selective transcription in response to an inflammatory stimulusStephen T Smale
Department of Microbiology, Immunology, and Molecular Genetics, Molecular Biology Institute, University of California, Los Angeles, 90095, USA
Cell 140:833-44. 2010..Toward this goal, recent studies have revealed an unexpected level of diversity in the mechanisms by which chromatin structure and individual transcription factors contribute to the selective regulation of inflammatory genes... - Seq-ing LPS-induced enhancersStephen T Smale
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Immunity 32:296-8. 2010..1 in enhancer marking... - The establishment and maintenance of lymphocyte identity through gene silencingStephen T Smale
Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095 1662, USA
Nat Immunol 4:607-15. 2003..This review surveys the current knowledge of gene silencing, with an emphasis on studies in lymphocytes that are advancing our general understanding of silencing mechanisms during development... - The RNA polymerase II core promoterStephen T Smale
Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095 1662, USA
Annu Rev Biochem 72:449-79. 2003..Although core promoter structure was originally thought to be invariant, a remarkable degree of diversity has become apparent. This article reviews the structural and functional diversity of the RNA polymerase II core promoter... - Pioneer factors in embryonic stem cells and differentiationStephen T Smale
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Curr Opin Genet Dev 20:519-26. 2010..These early interactions, which can lead to the presence of unmethylated CpG dinucleotides, histone modification signatures, and/or chromatin remodeling, may carry out different functions at different classes of genes... - Hierarchies of NF-κB target-gene regulationStephen T Smale
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA
Nat Immunol 12:689-94. 2011..This review summarizes the present knowledge and recent progress toward elucidating the numerous regulatory layers that confer target-gene selectivity in response to an NF-κB-inducing stimulus... - Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cellsJian Xu
Howard Hughes Medical Institute, Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
Proc Natl Acad Sci U S A 104:12377-82. 2007..The enhancer marks may therefore represent important features of the pluripotent state... - Assembly of silent chromatin during thymocyte developmentRuey-Chyi Su
Howard Hughes Medical Institute, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, USA
Semin Immunol 17:129-40. 2005..This article describes our findings in the context of current knowledge of gene silencing mechanisms... - A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodelingVladimir R Ramirez-Carrozzi
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Cell 138:114-28. 2009..By activating a diverse set of transcription factors, Toll-like receptors induce both classes and others for an optimal response to microbial pathogens... - Dynamic assembly of silent chromatin during thymocyte maturationRuey-Chyi Su
Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095-1662, USA
Nat Genet 36:502-6. 2004..In these cells, histone modification changes were nucleated at the promoter but did not spread. These results provide a foundation for elucidating the mechanisms of silent chromatin assembly during development... - Selective and antagonistic functions of SWI/SNF and Mi-2beta nucleosome remodeling complexes during an inflammatory responseVladimir R Ramirez-Carrozzi
Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095 1662, USA
Genes Dev 20:282-96. 2006..These results provide insight into the differential contributions of nucleosome remodeling complexes to the rapid induction of defined classes of mammalian genes and reveal a robust anti-inflammatory function of Mi-2beta... - A c-Rel subdomain responsible for enhanced DNA-binding affinity and selective gene activationShomyseh Sanjabi
Howard Hughes Medical Institute, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095 1662, USA
Genes Dev 19:2138-51. 2005.... - Interleukin-10 inhibits interleukin-12 p40 gene transcription by targeting a late event in the activation pathwayLiang Zhou
Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095-1662, USA
Mol Cell Biol 24:2385-96. 2004..These findings suggest that IL-10 blocks one or more events that occur after p40 locus decondensation and nucleosome remodeling and after, or in parallel with, the binding of a subset of p40 transcriptional activators... - A Th2 cytokine LCR. Adding a new piece to the regulatory puzzleStephen T Smale
Howard Hughes Medical Institute, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA
Immunity 19:1-2. 2003..As described in this issue of Immunity, Lee et al. have now used a transgenic mouse assay to identify a locus control region (LCR) that supports integration site-independent, copy number-dependent transcription of Il4 and Il13... - Pursuing gene regulation 'logic' via RNA interference and chromatin immunoprecipitationCaiyi C Li
Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1662, USA
Nat Immunol 7:692-7. 2006..Their combined use can help elucidate gene regulation 'logic' by aiding in target gene identification for transcription factors and chromatin-modifying complexes... - Transcriptional competence and the active marking of tissue-specific enhancers by defined transcription factors in embryonic and induced pluripotent stem cellsJian Xu
Molecular Biology Institute, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California at Los Angeles, Los Angeles, California 90095, USA
Genes Dev 23:2824-38. 2009..These results support the hypothesis that pluripotency and successful reprogramming may be critically dependent on the marking of enhancers for many or all tissue-specific genes... - Common interaction surfaces of the toll-like receptor 4 cytoplasmic domain stimulate multiple nuclear targetsTapani Ronni
Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California 90095, USA
Mol Cell Biol 23:2543-55. 2003..The mutant phenotypes provide a framework for future studies of TLR4 signaling, as the interaction supported by each critical surface residue will need to be defined... - C/EBPbeta regulation in lipopolysaccharide-stimulated macrophagesMichelle N Bradley
Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095 1662, USA
Mol Cell Biol 23:4841-58. 2003.... - Predominant interaction of both Ikaros and Helios with the NuRD complex in immature thymocytesRupa Sridharan
Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, California 90095, USA
J Biol Chem 282:30227-38. 2007..These results support the hypothesis that the NuRD complex makes major contributions to the functions of both Ikaros and Helios and that the activities of these proteins may be regulated in part by changes in phosphorylation... - An inducible enhancer required for Il12b promoter activity in an insulated chromatin environmentLiang Zhou
Howard Hughes Medical Institute, University of California Los Angeles, 675 Charles E Young Drive South, Los Angeles, CA 90095 1662, USA
Mol Cell Biol 27:2698-712. 2007..These results suggest that the HSS1 enhancer and Oct proteins play central roles in Il12b induction upon macrophage activation... - A common mechanism for mitotic inactivation of C2H2 zinc finger DNA-binding domainsSinisa Dovat
Howard Hughes Medical Institute, Department of Microbiology, Immunology, and Molecular Genetics, California 90095, USA
Genes Dev 16:2985-90. 2002..Phosphomimetic substitutions abolished DNA-binding and pericentromeric localization. A linker within Sp1 was also phosphorylated, suggesting that linker phosphorylation provides a global mechanism for inactivation of the C2H2 family... - Selective dimerization of a C2H2 zinc finger subfamilyAaron S McCarty
Howard Hughes Medical Institute, Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
Mol Cell 11:459-70. 2003..These results demonstrate that the C2H2 motif provides a versatile platform for both sequence-specific protein-nucleic acid interactions and highly specific dimerization... - Transgenic expression of Helios in B lineage cells alters B cell properties and promotes lymphomagenesisSinisa Dovat
Mattel Children s Hospital and Department of Pediatrics, University of California, Los Angeles, CA 90095, USA
J Immunol 175:3508-15. 2005..Taken together, these results demonstrate that silencing of Helios is critical for normal B cell function... - Ikaros DNA-binding proteins as integral components of B cell developmental-stage-specific regulatory circuitsElizabeth C Thompson
Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK
Immunity 26:335-44. 2007..Aiolos expression was controlled by pre-BCR signals via the adaptor protein SLP-65. Thus, pre-BCR signaling regulates Aiolos and the silencing of Igll1 via a developmental-stage-specific feedback loop... - Widespread failure of hematolymphoid differentiation caused by a recessive niche-filling allele of the Ikaros transcription factorPeter Papathanasiou
Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian National University, ACT 2601, Canberra, Australia
Immunity 19:131-44. 2003.... - Ikaros family members from the agnathan Myxine glutinosa and the urochordate Oikopleura dioica: emergence of an essential transcription factor for adaptive immunityPauline M Cupit
Sars International Centre for Marine Molecular Biology, High Technology Centre, Bergen, Norway
J Immunol 171:6006-13. 2003..glutinosa behaves as a true Ikaros family member. Taken together, these results indicate that the properties associated with the Ikaros family preceded the emergence of the jawed vertebrates and thus adaptive immunity... - Upstream of IkarosDavid Liberg
Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, W12 0NN, London, UK
Trends Immunol 24:567-70. 2003..Each cell type is defined by lineage-specific patterns of gene expression. The DNA binding protein Ikaros is an important regulator of haematopoiesis and recent work promises to shed light on how Ikaros itself is regulated... - Hematopoiesis flies high with IkarosStephen T Smale
Nat Immunol 7:367-9. 2006 - Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IkappaBzetaHisako Kayama
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565 0871, Japan
J Biol Chem 283:12468-77. 2008..These mechanistic distinctions advance our understanding of the diverse molecular cascades that underlie the differential regulation of pro-inflammatory genes... - Epigenetic characterization of hematopoietic stem cell differentiation using miniChIP and bisulfite sequencing analysisJoanne L Attema
Institute of Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
Proc Natl Acad Sci U S A 104:12371-6. 2007..Together, these data support a model in which epigenetic modifications serve as an important mechanism to control HSC multipotency... - T cell lineage choice and differentiation in the absence of the RNase III enzyme DicerBradley S Cobb
Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, England, UK
J Exp Med 201:1367-73. 2005..Thus, although Dicer seems to be critical for the development of the early embryo, it may have limited impact on the implementation of some lineage-specific gene expression programs...
Research Grants
- REGULATION OF TDT EXPRESSION DURING LYMPHOPOIESISSTEPHEN SMALE; Fiscal Year: 2009..abstract_text> ..
- Selective gene activation by the NF-kappaB family of transcription factorsStephen T Smale; Fiscal Year: 2010....
- Pro-inflammatory gene regulation in a native chromatin environmentStephen T Smale; Fiscal Year: 2010..The long-term goal of this research is to develop strategies for the selective modulation of pro-inflammatory genes in the context of human disease. ..
- Selective gene activation by the NF-kappaB family of transcription factorsSTEPHEN SMALE; Fiscal Year: 2007....
- REGULATION OF TDT EXPRESSION DURING LYMPHOPOIESISSTEPHEN SMALE; Fiscal Year: 1999..Eventually, the investigators hope to use the knowledge generated during these studies to elucidate the molecular events that regulate early lymphoid development and the fetal/adult lymphopoietic transition. ..
- REGULATION OF TDT EXPRESSION DURING LYMPHOPOIESISSTEPHEN SMALE; Fiscal Year: 2004..Finally, to examine the relevance of Ikaros for gene inactivation in lymphocytes, mouse strains allowing the conditional disruption of the Ikaros gene are being prepared. ..
- MEDICAL SCIENTIST TRAINING PROGRAMSTEPHEN SMALE; Fiscal Year: 2007..Both institutions are actively recruiting new faculty to fulfill their research missions and to train new, young scientists. ..
- Selective Regulation of Pro-inflammatory Genes in MacrophagesStephen T Smale; Fiscal Year: 2010..The long-term goal of this research is to develop pharmacologic strategies for the selective modulation of pro-inflammatory genes, leading to the enhanced expression of protective genes and reduced expression of detrimental genes. ..