Chromatin Accessibility Dynamics during iPSC Reprogramming

Publication date: 7 December 2017
Source:Cell Stem Cell, Volume 21, Issue 6
Author(s): Dongwei Li, Jing Liu, Xuejie Yang, Chunhua Zhou, Jing Guo, Chuman Wu, Yue Qin, Lin Guo, Jiangping He, Shenyong Yu, He Liu, Xiaoshan Wang, Fang Wu, Junqi Kuang, Andrew P. Hutchins, Jiekai Chen, Duanqing Pei
Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC-seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in chromatin states shifting from open to closed (OC) and closed to open (CO), with an initial burst of OC and an ending surge of CO. The OC loci are largely composed of genes associated with a somatic fate, while the CO loci are associated with pluripotency. Factors/conditions known to impede reprogramming prevent OSK-driven OC and skew OC-CO dynamics. While the CO loci are enriched for OSK motifs, the OC loci are not, suggesting alternative mechanisms for chromatin closing. Sap30, a Sin3A corepressor complex component, is required for the OC shift and facilitates reduced H3K27ac deposition at OC loci. These results reveal a chromatin accessibility logic during reprogramming that may apply to other cell-fate decisions.

Graphical abstract

Teaser

Li et al. show that Yamanaka factors remodel the nuclear architecture of MEFs following a binary logic that may guide further improvement in reprograming technology and be applicable for other cell-fate decisions.


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