Enhancer priming by H3K4 methyltransferase MLL4 controls cell fate transition

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• Lee, Ji-Eun
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• Lai, Binbin
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• Macfarlan, Todd S.
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• Xu, Shiliyang
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• Zhuang, Lenan
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• Liu, Chengyu
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• Peng, Weiqun
;
• Ge, Kai

Abstract

Transcriptional enhancers control cell-identity gene expression and thus determine cell identity. Enhancers are primed by histone H3K4 mono-/di-methyltransferase MLL4 before they are activated by histone H3K27 acetyltransferase p300. Here, we show that MLL4 is dispensable for cell-identity maintenance but essential for cell fate transition using several model systems including embryonic stem cell (ESC) differentiation toward somatic cells and somatic cell reprogramming into ESC-like cells. Mechanistically, MLL4 is dispensable for maintaining p300 binding on active enhancers of cell-identity genes but is required for p300 binding on enhancers activated during cell fate transition. These results indicate that, although enhancer priming by MLL4 is dispensable for cell-identity maintenance, it controls cell fate transition by orchestrating p300-mediated enhancer activation.