1. Stepwise de novo establishment of inactive X chromosome architecture in early development
- Author
-
Du, Zhenhai, Hu, Liangjun, Zou, Zhuoning, Liu, Meishuo, Li, Zihan, Lu, Xukun, Harris, Clair, Xiang, Yunlong, Chen, Fengling, Yu, Guang, Xu, Kai, Kong, Feng, Xu, Qianhua, Huang, Bo, Liu, Ling, Fan, Qiang, Wang, Haifeng, Kalantry, Sundeep, and Xie, Wei
- Abstract
X chromosome inactivation triggers a dramatic reprogramming of transcription and chromosome architecture. However, how the chromatin organization of inactive X chromosome is established de novo in vivo remains elusive. Here, we identified an Xist-separated megadomain structure (X-megadomains) on the inactive X chromosome in mouse extraembryonic lineages and extraembryonic endoderm (XEN) cell lines, and transiently in the embryonic lineages, before Dxz4-delineated megadomain formation at later stages in a strain-specific manner. X-megadomain boundary coincides with strong enhancer activities and cohesin binding in an Xistregulatory region required for proper Xistactivation in early embryos. Xistregulatory region disruption or cohesin degradation impaired X-megadomains in extraembryonic endoderm cells and caused ectopic activation of regulatory elements and genes near Xist, indicating that cohesin loading at regulatory elements promotes X-megadomains and confines local gene activities. These data reveal stepwise X chromosome folding and transcriptional regulation to achieve both essential gene activation and global silencing during the early stages of X chromosome inactivation.
- Published
- 2024
- Full Text
- View/download PDF