【百文】【文献通读】The Pioneer Transcription Factor FoxA Maintains an Accessible Nucleosome Configuration ...

Author：Makiko Iwafuchi-Doi, Greg Donahue, Akshay Kakumanu, ..., Dolim Lee, Klaus H. Kaestner, Kenneth S. Zaret

Abstract：Nuclear DNA wraps around core histones to form
nucleosomes, which restricts the binding of tran-
scription 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 micrococcal
nuclease (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 tran-
scription factors, are retained more at liver-specific
enhancers than at promoters and ubiquitous en-
hancers. 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.

Publisher URL: http://dx.doi.org/10.1016/j.molcel.2016.03.001

背景：
理论基础：PTF结合到核小体，引起基因转录，染色质局部打开。

科学问题：
开放染色质的核小体结构及其调控的基础尚不清楚。

样本：
Mouse liver

主要实验方法：
low/high Mnase-seq；ChIP-exo; DNase-seq; ChIP-qPCR;

结果:

1. Liver特异性enhancer大于普遍enhancer的核小体开放性
2. FoxA通过取代H1结合到核小体，且保持开放性；
3. FoxA2与其他liver TFs共同结合到核小体开放区dyad axis附近
4. FoxA结合到核小体enhancer引起基因活性

讨论：
怎么定义的enhancer？
提出模型，通过敲除关键TF验证：

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