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PMID: 20620946 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation.

Immunity ·Vol. 32 ·No. 6 ·2010-06-25 ·Pages 840-51

Wei L, Vahedi G, Sun HW, Watford WT, Takatori H, Ramos HL, Takahashi H, Liang J, Gutierrez-Cruz G, Zang C, Peng W, O'Shea JJ, Kanno Y

Abstract

Signal transducer and activator of transcription 4 (STAT4) and STAT6 are key factors in the specification of helper T cells; however, their direct roles in driving differentiation are not well understood. Using chromatin immunoprecipitation and massive parallel sequencing, we quantitated the full complement of STAT-bound genes, concurrently assessing global STAT-dependent epigenetic modifications and gene transcription by using cells from cognate STAT-deficient mice. STAT4 and STAT6 each bound over 4000 genes with distinct binding motifs. Both played critical roles in maintaining chromatin configuration and transcription of a core subset of genes through the combination of different epigenetic patterns. Globally, STAT4 had a more dominant role in promoting active epigenetic marks, whereas STAT6 had a more prominent role in antagonizing repressive marks. Clusters of genes negatively regulated by STATs were also identified, highlighting previously unappreciated repressive roles of STATs. Therefore, STAT4 and STAT6 play wide regulatory roles in T helper cell specification.

MeSH Terms
Animals Cell Differentiation/immunology Chromatin Immunoprecipitation Epigenesis, Genetic Gene Expression Gene Expression Regulation/immunology Mice Mice, Inbred C57BL Mice, Knockout Oligonucleotide Array Sequence Analysis STAT4 Transcription Factor/genetics,immunology STAT6 Transcription Factor/genetics,immunology T-Lymphocytes, Helper-Inducer/cytology,immunology,metabolism Transcription, Genetic
Chemicals
STAT4 Transcription Factor STAT6 Transcription Factor
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Wei Lai
Molecular Immunology and Inflammation Branch, NIAMS, National Institutes of Health, Bethesda MD 20892, USA.
Vahedi Golnaz
Sun Hong-Wei
Watford Wendy T
Takatori Hiroaki
Ramos Haydee L
Takahashi Hayato
Liang Jonathan
Gutierrez-Cruz Gustavo
Zang Chongzhi
Peng Weiqun
O'Shea John J
Kanno Yuka
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2010.06.003
Published
2010-06-25
Pages
840-51
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2904651
Subset
IM
Grants
Intramural NIH HHS · Z99 AR999999 · United States
Databases
GEO
GSE22105
External Links
PubMed source DOI: 10.1016/j.immuni.2010.06.003 PMC Full Text View journal details
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