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

Lai Wei, Golnaz Vahedi, Hong Wei Sun, Wendy T. Watford, Hiroaki Takatori, Haydee L. Ramos, Hayato Takahashi, Jonathan Liang, Gustavo Gutierrez-Cruz, Chongzhi Zang, Weiqun Peng, John J. O'Shea, Yuka Kanno

Research output: Contribution to journalArticlepeer-review

231 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)840-851
Number of pages12
JournalImmunity
Volume32
Issue number6
DOIs
Publication statusPublished - 2010 Jun
Externally publishedYes

Keywords

  • MOLIMMUNO
  • SYSBIO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation'. Together they form a unique fingerprint.

Cite this