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：
理論基礎(chǔ)：PTF結(jié)合到核小體，引起基因轉(zhuǎn)錄身腻，染色質(zhì)局部打開宠页。
科學(xué)問題：
開放染色質(zhì)的核小體結(jié)構(gòu)及其調(diào)控的基礎(chǔ)尚不清楚檬嘀。
樣本：
Mouse liver
主要實(shí)驗(yàn)方法：
low/high Mnase-seq；ChIP-exo; DNase-seq; ChIP-qPCR;
結(jié)果:
- Liver特異性enhancer大于普遍enhancer的核小體開放性
- FoxA通過取代H1結(jié)合到核小體涂身，且保持開放性娃肿；
- FoxA2與其他liver TFs共同結(jié)合到核小體開放區(qū)dyad axis附近
- FoxA結(jié)合到核小體enhancer引起基因活性
討論：
怎么定義的enhancer？
提出模型外厂，通過敲除關(guān)鍵TF驗(yàn)證：
