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

• Published in: Nature communications Vol. 13; no. 1; p. 1293
• Main Authors: Li, Mingsen, Huang, Huaxing, Wang, Bofeng, Jiang, Shaoshuai, Guo, Huizhen, Zhu, Liqiong, Wu, Siqi, Liu, Jiafeng, Wang, Li, Lan, Xihong, Zhang, Wang, Zhu, Jin, Li, Fuxi, Tan, Jieying, Mao, Zhen, Liu, Chunqiao, Ji, Jianping, Ding, Junjun, Zhang, Kang, Yuan, Jin, Liu, Yizhi, Ouyang, Hong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.03.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 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
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28966-6

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.