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Nucleic Acids Res. 2013 Feb 1;41(4):2155-70. doi: 10.1093/nar/gks1300. Epub 2013 Jan 7.

Distinct transcriptional regulatory modules underlie STAT3's cell type-independent and cell type-specific functions.

Author information

1
World Premier International (WPI) Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita, 565-0871 Osaka, Japan.

Abstract

Transcription factors (TFs) regulate gene expression by binding to short DNA sequence motifs, yet their binding specificities alone cannot explain how certain TFs drive a diversity of biological processes. In order to investigate the factors that control the functions of the pleiotropic TF STAT3, we studied its genome-wide binding patterns in four different cell types: embryonic stem cells, CD4(+) T cells, macrophages and AtT-20 cells. We describe for the first time two distinct modes of STAT3 binding. First, a small cell type-independent mode represented by a set of 35 evolutionarily conserved STAT3-binding sites that collectively regulate STAT3's own functions and cell growth. We show that STAT3 is recruited to sites with E2F1 already pre-bound before STAT3 activation. Second, a series of different transcriptional regulatory modules (TRMs) assemble around STAT3 to drive distinct transcriptional programs in the four cell types. These modules recognize cell type-specific binding sites and are associated with factors particular to each cell type. Our study illustrates the versatility of STAT3 to regulate both universal- and cell type-specific functions by means of distinct TRMs, a mechanism that might be common to other pleiotropic TFs.

PMID:
23295670
PMCID:
PMC3575808
DOI:
10.1093/nar/gks1300
[Indexed for MEDLINE]
Free PMC Article
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