The Pioneer Transcription Factor FoxA Maintains an Accessible Nucleosome Configuration at Enhancers for Tissue-Specific Gene Activation.
The Pioneer Transcription Factor FoxA Maintains an Accessible Nucleosome Configuration at Enhancers for Tissue-Specific Gene Activation.
复制标题
先锋转录因子FOXA在增强子方面维持可访问的核小体构型，用于组织特异性基因激活。
DOI：
10.1016/j.molcel.2016.03.001
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发表时间：
2016-04-07
期刊：
影响因子：
16
通讯作者：
Zaret KS
中科院分区：
文献类型：
--
作者：
Iwafuchi-Doi M;Donahue G;Kakumanu A;Watts JA;Mahony S;Pugh BF;Lee D;Kaestner KH;Zaret KS
Nuclear DNA wraps around core histones to form nucleosomes, which restricts the binding of transcription factors to gene regulatory sequences. Pioneer transcription factors can bind DNA sites on nucleosomes and initiate gene regulatory events, often leading to the local opening of chromatin. However, the nucleosomal configuration of open chromatin and the basis for its regulation is unclear. We combined low and high levels of MNase digestion along with core histone mapping to assess the nucleosomal configuration at enhancers and promoters in mouse liver. We find that MNase-accessible nucleosomes, bound by transcription factors, are retained more at liver-specific enhancers than at promoters and ubiquitous enhancers. The pioneer factor FoxA displaces linker histone H1, thereby keeping enhancer nucleosomes accessible in chromatin and allowing other liver-specific transcription factors to bind and stimulate transcription. Thus, nucleosomes are not exclusively repressive to gene regulation when they are retained with, and exposed by, pioneer factors.
