BMP4 resets mouse epiblast stem cells to naive pluripotency through ZBTB7A/B-mediated chromatin remodelling.,Nature Cell Biology

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BMP4 resets mouse epiblast stem cells to naive pluripotency through ZBTB7A/B-mediated chromatin remodelling.
Nature Cell Biology ( IF 17.3 ) Pub Date : 2020-05-11 , DOI: 10.1038/s41556-020-0516-x
Shengyong Yu _{1,

2,

3,

4} , Chunhua Zhou _{1,

2,

3,

4} , Shangtao Cao _{1,

2,

4} , Jiangping He _{1,

2,

3,

4} , Baomei Cai _{1,

2,

3,

4} , Kaixin Wu _{1,

2,

3} , Yue Qin _{1,

2,

3,

4} , Xingnan Huang _{1,

5} , Lizhan Xiao _{1,

2,

3} , Jing Ye _{1,

2,

4} , Shuyang Xu _{1,

2,

3,

4} , Wenxiu Xie _{1,

2,

4} , Junqi Kuang _{1,

2,

3,

4} , Shilong Chu _{1,

2,

4} , Jing Guo _{1,

2,

4} , He Liu _{1,

2,

4} , Wei Pang _{1,

2,

4} , Lin Guo _{1,

2,

4} , Mengying Zeng _{1,

2,

4} , Xiaoshan Wang _{1,

2,

4,

5} , Rongping Luo _{1,

2,

4} , Chen Li _{1,

2,

4} , Guoqing Zhao _{1,

3,

4,

6} , Bo Wang _{1,

2,

4} , Linlin Wu _{1,

2,

4} , Jiekai Chen _{1,

2,

4,

5,

6} , Jing Liu _{1,

2,

4,

5,

6} , Duanqing Pei _{1,

2,

4,

5,

6}

Affiliation

BMP4 regulates a plethora of developmental processes, including the dorsal-ventral axis and neural patterning. Here, we report that BMP4 reconfigures the nuclear architecture during the primed-to-naive transition (PNT). We first established a BMP4-driven PNT and show that BMP4 orchestrates the chromatin accessibility dynamics during PNT. Among the loci opened early by BMP4, we identified Zbtb7a and Zbtb7b (Zbtb7a/b) as targets that drive PNT. ZBTB7A/B in turn facilitate the opening of naive pluripotent chromatin loci and the activation of nearby genes. Mechanistically, ZBTB7A not only binds to chromatin loci near to the genes that are activated, but also strategically occupies those that are silenced, consistent with a role of BMP4 in both activating and suppressing gene expression during PNT at the chromatin level. Our results reveal a previously unknown function of BMP4 in regulating nuclear architecture and link its targets ZBTB7A/B to chromatin remodelling and pluripotent fate control.

中文翻译：

BMP4通过ZBTB7A / B介导的染色质重塑将小鼠表皮干细胞重置为幼稚多能性。

BMP4调节过多的发育过程，包括背腹轴和神经模式。在这里，我们报告说，BMP4在准备好的天真过渡（PNT）期间重新配置了核体系结构。我们首先建立了由BMP4驱动的PNT，并显示BMP4在PNT期间协调了染色质可及性动态。在BMP4早期开放的基因座中，我们确定Zbtb7a和Zbtb7b（Zbtb7a / b）是驱动PNT的靶标。ZBTB7A / B进而促进了幼稚多能染色质基因座的开放和附近基因的激活。从机制上讲，ZBTB7A不仅与活化基因附近的染色质基因座结合，而且在战略上占据沉默的基因，这与BMP4在染色质水平的PNT活化和抑制基因表达中的作用一致。

更新日期：2020-05-11

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