Chromatin Accessibility Dynamics during iPSC Reprogramming

作者：Li, Dongwei; Liu, Jing; Yang, Xuejie; Zhou, Chunhua; Guo, Jing; Wu, Chuman; Qin, Yue; Guo, Lin; He, Jiangping; Yu, Shenyong; Liu, He; Wang, Xiaoshan; Wu, Fang; Kuang, Junqi; Hutchins, Andrew P.; Chen, Jiekai; Pei, Duanqing

来源：Cell Stem Cell, 2017, 21(6): 819-+.

DOI：10.1016/j.stem.2017.10.012

• PLURIPOTENT STEM-CELLS
• GLOBAL GENE-EXPRESSION
• DEEP-SEQUENCING DATA
• RNA-SEQ DATA
• SOMATIC-CELLS
• GENOME
• INDUCTION
• BINDING
• MOUSE
• OCT4

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 OSKdriven 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 andfacilitates reduced H3K27ac deposition at OC loci. These results reveal a chromatin accessibility logic during reprogramming that may apply to other cell-fate decisions.

• 单位
  中国科学院; 中国科学院大学; 广州医科大学