期刊
NUCLEIC ACIDS RESEARCH
卷 41, 期 4, 页码 2155-2170出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gks1300
关键词
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资金
- Japan Society for the Promotion of Science (JSPS)
- Kishimoto Foundation
- ETHZ-JST Japanese-Swiss Cooperative Program
- Jeanne and Jean-Louis Levesque Chair in Cancer Research and Canadian Cancer Society Research Institute [700922]
- JSPS
- Grants-in-Aid for Scientific Research [22500277] Funding Source: KAKEN
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.
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