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Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs
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DOI：10.1038/s41467-018-03748-1.png)
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摘要
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Multicellular organisms consist of multiple cell types. The identity of these cells is primarily maintained by cell-type-specific gene expression programs; however, mechanisms that suppress these programs are poorly defined. Here we show that serum response factor (Srf), a transcription factor that is activated by various extracellular stimuli, can repress cell-type specific genes and promote cellular reprogramming to pluripotency. Manipulations that decrease beta-actin monomer quantity result in the nuclear accumulation of Mkl1 and the activation of Srf, which downregulate cell-type-specific genes and alter the epigenetics of regulatory regions and chromatin organization. Mice overexpressing Srf exhibit various pathologies including an ulcerative colitis-like symptom and a metaplasia-like phenotype in the pancreas. Our results demonstrate an unexpected function of Srf via a mechanism by which extracellular stimuli actively destabilize cell identity and suggest Srf involvement in a wide range of diseases.
Keyword:
SERUM RESPONSE FACTOR
EMBRYONIC STEM-CELLS
FACTOR-BINDING SITES
TRANSCRIPTION FACTORS
SUPER-ENHANCERS
READ ALIGNMENT
ACTIN
DIFFERENTIATION
PLURIPOTENCY
ACTIVATION
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IF:
15.7
论文数:
9.4W
被引数:
91.2W
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