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Chromatin Accessibility Dynamics During Reprogramming

37 Pages Posted: 4 Apr 2018 Sneak Peek Status: Published

See all articles by Dongwei Li

Dongwei Li

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Jing Liu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Xuejie Yang

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Chunhua Zhou

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Jing Guo

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Yue Qin

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Lin Guo

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

He Liu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Xiaoshan Wang

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Fang Wu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Junqi Kuang

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Yuanbin Cui

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Jiangping He

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Andrew P. Hutchins

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Jiekai Chen

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Duanqing Pei

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

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Abstract

Cell fate decisions remain poorly understood at the chromatin level. Here we report a dynamic logic for chromatin remodeling during reprogramming. Global mapping of accessible chromatin loci in MEFs expressing Oct4-Sox2-Klf4 by ATAC-seq reveals dynamic changes from open to closed (OC) and closed to open (CO), with a burst of OC in the beginning and a climax CO at the end. We then show that factors/conditions known to impede reprogramming prevent OSK-driven OC and skew the overall OC-CO dynamics. Mechanistically, while the CO loci are enriched with and opened by Oct4-Sox2-Klf4 directly, the OC loci are devoid of them suggesting an indirect OC process. Indeed, we show that Sap30 is activated early and plays a key role in the OC process. These results reveal a chromatin accessibility logic during reprogramming and identify Sap30 as one of the first responders critical for the prerequisite silencing of somatic genes.

Suggested Citation

Li, Dongwei and Liu, Jing and Yang, Xuejie and Zhou, Chunhua and Guo, Jing and Qin, Yue and Guo, Lin and Liu, He and Wang, Xiaoshan and Wu, Fang and Kuang, Junqi and Cui, Yuanbin and He, Jiangping and Hutchins, Andrew P. and Chen, Jiekai and Pei, Duanqing, Chromatin Accessibility Dynamics During Reprogramming (2018). Available at SSRN: https://ssrn.com/abstract=3155968 or http://dx.doi.org/10.2139/ssrn.3155968
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Dongwei Li (Contact Author)

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Jing Liu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Xuejie Yang

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Chunhua Zhou

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Jing Guo

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Yue Qin

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Lin Guo

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

He Liu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Xiaoshan Wang

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Fang Wu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Junqi Kuang

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Yuanbin Cui

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Jiangping He

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Andrew P. Hutchins

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Jiekai Chen

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Duanqing Pei

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

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