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

© 2022. The Author(s)..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

Nature communications - 13(2022), 1 vom: 11. März, Seite 1293

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

CCCTC-Binding Factor
Chromatin
Journal Article
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 05.04.2022

Date Revised 10.11.2022

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41467-022-28966-6

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM338083197