STEPHEN SMALE

Summary

Affiliation: University of California
Country: USA

Publications

  1. ncbi request reprint Chromatin structure and gene regulation in the immune system
    Stephen 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
  2. doi request reprint Chromatin contributions to the regulation of innate immunity
    Stephen T Smale
    Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095 email
    Annu Rev Immunol 32:489-511. 2014
  3. doi request reprint Dimer-specific regulatory mechanisms within the NF-κB family of transcription factors
    Stephen T Smale
    Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
    Immunol Rev 246:193-204. 2012
  4. pmc Transcriptional regulation in the innate immune system
    Stephen T Smale
    Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
    Curr Opin Immunol 24:51-7. 2012
  5. pmc Selective transcription in response to an inflammatory stimulus
    Stephen T Smale
    Department of Microbiology, Immunology, and Molecular Genetics, Molecular Biology Institute, University of California, Los Angeles, 90095, USA
    Cell 140:833-44. 2010
  6. doi request reprint Seq-ing LPS-induced enhancers
    Stephen T Smale
    Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
    Immunity 32:296-8. 2010
  7. pmc Pioneer factors in embryonic stem cells and differentiation
    Stephen 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
  8. ncbi request reprint The establishment and maintenance of lymphocyte identity through gene silencing
    Stephen 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
  9. ncbi request reprint The RNA polymerase II core promoter
    Stephen 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
  10. pmc Hierarchies of NF-κB target-gene regulation
    Stephen T Smale
    Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA
    Nat Immunol 12:689-94. 2011

Collaborators

Detail Information

Publications35

  1. ncbi request reprint Chromatin structure and gene regulation in the immune system
    Stephen 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...
  2. doi request reprint Chromatin contributions to the regulation of innate immunity
    Stephen T Smale
    Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095 email
    Annu Rev Immunol 32:489-511. 2014
    ..These findings have generated interest in the capacity to modulate chromatin regulators with small-molecule compounds for the treatment of diseases associated with innate or adaptive immunity. ..
  3. doi request reprint Dimer-specific regulatory mechanisms within the NF-κB family of transcription factors
    Stephen 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...
  4. pmc Transcriptional regulation in the innate immune system
    Stephen T Smale
    Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
    Curr Opin Immunol 24:51-7. 2012
    ....
  5. pmc Selective transcription in response to an inflammatory stimulus
    Stephen 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...
  6. doi request reprint Seq-ing LPS-induced enhancers
    Stephen 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...
  7. pmc Pioneer factors in embryonic stem cells and differentiation
    Stephen 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...
  8. ncbi request reprint The establishment and maintenance of lymphocyte identity through gene silencing
    Stephen 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...
  9. ncbi request reprint The RNA polymerase II core promoter
    Stephen 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...
  10. pmc Hierarchies of NF-κB target-gene regulation
    Stephen 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...
  11. pmc Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells
    Jian 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...
  12. ncbi request reprint Assembly of silent chromatin during thymocyte development
    Ruey 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...
  13. pmc A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling
    Vladimir 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...
  14. ncbi request reprint Dynamic assembly of silent chromatin during thymocyte maturation
    Ruey 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...
  15. pmc Selective and antagonistic functions of SWI/SNF and Mi-2beta nucleosome remodeling complexes during an inflammatory response
    Vladimir 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...
  16. pmc A c-Rel subdomain responsible for enhanced DNA-binding affinity and selective gene activation
    Shomyseh 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
    ....
  17. ncbi request reprint A Th2 cytokine LCR. Adding a new piece to the regulatory puzzle
    Stephen 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...
  18. pmc Interleukin-10 inhibits interleukin-12 p40 gene transcription by targeting a late event in the activation pathway
    Liang 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...
  19. pmc Transcriptional competence and the active marking of tissue-specific enhancers by defined transcription factors in embryonic and induced pluripotent stem cells
    Jian 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...
  20. ncbi request reprint Pursuing gene regulation 'logic' via RNA interference and chromatin immunoprecipitation
    Caiyi 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...
  21. pmc Common interaction surfaces of the toll-like receptor 4 cytoplasmic domain stimulate multiple nuclear targets
    Tapani 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...
  22. pmc C/EBPbeta regulation in lipopolysaccharide-stimulated macrophages
    Michelle 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
    ....
  23. ncbi request reprint Predominant interaction of both Ikaros and Helios with the NuRD complex in immature thymocytes
    Rupa 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...
  24. pmc An inducible enhancer required for Il12b promoter activity in an insulated chromatin environment
    Liang 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...
  25. ncbi request reprint Selective dimerization of a C2H2 zinc finger subfamily
    Aaron 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...
  26. pmc A common mechanism for mitotic inactivation of C2H2 zinc finger DNA-binding domains
    Sinisa 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...
  27. ncbi request reprint Transgenic expression of Helios in B lineage cells alters B cell properties and promotes lymphomagenesis
    Sinisa 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...
  28. ncbi request reprint Widespread failure of hematolymphoid differentiation caused by a recessive niche-filling allele of the Ikaros transcription factor
    Peter 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
    ....
  29. ncbi request reprint Ikaros family members from the agnathan Myxine glutinosa and the urochordate Oikopleura dioica: emergence of an essential transcription factor for adaptive immunity
    Pauline 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...
  30. ncbi request reprint Ikaros DNA-binding proteins as integral components of B cell developmental-stage-specific regulatory circuits
    Elizabeth 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...
  31. ncbi request reprint Upstream of Ikaros
    David 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...
  32. pmc Epigenetic characterization of hematopoietic stem cell differentiation using miniChIP and bisulfite sequencing analysis
    Joanne 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...
  33. ncbi request reprint Hematopoiesis flies high with Ikaros
    Stephen T Smale
    Nat Immunol 7:367-9. 2006
  34. pmc T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer
    Bradley 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...
  35. doi request reprint Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IkappaBzeta
    Hisako 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...

Research Grants27

  1. REGULATION OF TDT EXPRESSION DURING LYMPHOPOIESIS
    STEPHEN SMALE; Fiscal Year: 2009
    ..abstract_text> ..
  2. Selective gene activation by the NF-kappaB family of transcription factors
    Stephen T Smale; Fiscal Year: 2010
    ....
  3. Pro-inflammatory gene regulation in a native chromatin environment
    Stephen 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. ..
  4. Selective gene activation by the NF-kappaB family of transcription factors
    STEPHEN SMALE; Fiscal Year: 2007
    ....
  5. REGULATION OF TDT EXPRESSION DURING LYMPHOPOIESIS
    STEPHEN 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. ..
  6. REGULATION OF TDT EXPRESSION DURING LYMPHOPOIESIS
    STEPHEN 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. ..
  7. MEDICAL SCIENTIST TRAINING PROGRAM
    STEPHEN SMALE; Fiscal Year: 2007
    ..Both institutions are actively recruiting new faculty to fulfill their research missions and to train new, young scientists. ..
  8. Selective Regulation of Pro-inflammatory Genes in Macrophages
    Stephen 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. ..