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

Mingsen Li, Huaxing Huang, Bofeng Wang, Shaoshuai Jiang, Huizhen Guo, Liqiong Zhu, Siqi Wu, Jiafeng Liu, Li Wang, Xihong Lan, Wang Zhang, Jin Zhu, Fuxi Li, Jieying Tan, Zhen Mao, Chunqiao Liu, Jianping Ji, Junjun Ding, Kang Zhang, Jin Yuan, Yizhi Liu () and Hong Ouyang ()
Additional contact information
Mingsen Li: Sun Yat-sen University
Huaxing Huang: Sun Yat-sen University
Bofeng Wang: Sun Yat-sen University
Shaoshuai Jiang: Sun Yat-Sen University
Huizhen Guo: Sun Yat-sen University
Liqiong Zhu: Sun Yat-sen University
Siqi Wu: Sun Yat-sen University
Jiafeng Liu: Sun Yat-sen University
Li Wang: Sun Yat-sen University
Xihong Lan: Sun Yat-sen University
Wang Zhang: Sun Yat-sen University
Jin Zhu: Sun Yat-sen University
Fuxi Li: Sun Yat-sen University
Jieying Tan: Sun Yat-sen University
Zhen Mao: Sun Yat-sen University
Chunqiao Liu: Sun Yat-sen University
Jianping Ji: Sun Yat-sen University
Junjun Ding: Sun Yat-Sen University
Kang Zhang: Macau University of Science and Technology
Jin Yuan: Sun Yat-sen University
Yizhi Liu: Sun Yat-sen University
Hong Ouyang: Sun Yat-sen University

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-28966-6

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