Journal Article

Comprehensive 3D epigenomic maps define limbal stem/progenitor cell function and identity

Lan, Xihong, Zhu, Jin, Ouyang, Hong, Wang, Li, Liu, Chunqiao, Zhang, Kang, Ding, Junjun, Liu, Jiafeng, Zhang, Wang, Guo, Huizhen, Li, Mingsen, Li, Fuxi, Tan, Jieying, Liu, Yizhi, Ji, Jianping, Yuan, Jin, Wang, Bofeng, Mao, Zhen, Jiang, Shaoshuai, Huang, Huaxing, Zhu, Liqiong, Wu, Siqi

2022

Overview

The insights into how genome topology couples with epigenetic states to govern the function and identity of the corneal epithelium are poorly understood. Here, we generate a high-resolution Hi-C interaction map of human limbal stem/progenitor cells (LSCs) and show that chromatin multi-hierarchical organisation is coupled to gene expression. By integrating Hi-C, epigenome and transcriptome data, we characterize the comprehensive 3D epigenomic landscapes of LSCs. We find that super-silencers mediate gene repression associated with corneal development, differentiation and disease via chromatin looping and/or proximity. Super-enhancer (SE) interaction analysis identified a set of SE interactive hubs that contribute to LSC-specific gene activation. These active and inactive element-anchored loop networks occur within the cohesin-occupied CTCF-CTCF loops. We further reveal a coordinated regulatory network of core transcription factors based on SE-promoter interactions. Our results provide detailed insights into the genome organization principle for epigenetic regulation of gene expression in stratified epithelia. Genome topology provides a structural basis for epigenome-mediated transcriptional regulation in eukaryotes. Here the authors characterized the 3D genome of stratified squamous epithelia. They generated a Hi-C map of human limbal stem/progenitor cells (LSCs) and integrated these data with epigenomics, transcription factor binding maps, and transcriptome data.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45/15 / 45/23 / 631/337/100 / 631/532/2118 / CCCTC-Binding Factor - metabolism / Cells (biology) / Chromatin / Chromatin - genetics / Cohesin / Cornea / Epigenesis, Genetic / Epigenetics / Epigenomics / Epithelium / Eukaryotes / Gene expression / Gene mapping / Gene regulation / Genomes / Humanities and Social Sciences / Humans / multidisciplinary / Network topologies / Progenitor cells / Promoter Regions, Genetic - genetics / Science / Science (multidisciplinary) / Stem cells / Stem Cells - metabolism / Stems / Topology / Transcription factors / Transcriptomes