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LncRNA Mrhl orchestrates differentiation programs in mouse embryonic stem cells through chromatin mediated regulation

Pal, Debosree; Neha, CV; Bhaduri, Utsa; Zenia, Zenia; Dutta, Sangeeta; Chidambaram, Subbulakshmi; Rao, MRS; (2021) LncRNA Mrhl orchestrates differentiation programs in mouse embryonic stem cells through chromatin mediated regulation. Stem Cell Research , 53 , Article 102250. 10.1016/j.scr.2021.102250. Green open access

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Abstract

Long non-coding RNAs (lncRNAs) have been well-established to act as regulators and mediators of development and cell fate specification programs. LncRNA Mrhl (meiotic recombination hotspot locus) has been shown to act in a negative feedback loop with WNT signaling to regulate male germ cell meiotic commitment. In our current study, we have addressed the role of Mrhl in development and differentiation using mouse embryonic stem cells (mESCs) as our model system of study. Mrhl is a nuclear-localized, chromatin-bound lncRNA with moderately stable expression in mESCs. Transcriptome analyses and loss-of-function phenotype studies revealed dysregulation of developmental processes, lineage-specific transcription factors and key networks along with aberrance in specification of early lineages during differentiation of mESCs. Genome-wide chromatin occupancy studies suggest regulation of chromatin architecture at key target loci through triplex formation. Our studies thus reveal a role for lncRNA Mrhl in regulating differentiation programs in mESCs in the context of appropriate cues through chromatin-mediated responses.

Type: Article
Title: LncRNA Mrhl orchestrates differentiation programs in mouse embryonic stem cells through chromatin mediated regulation
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.scr.2021.102250
Publisher version: https://doi.org/10.1016/j.scr.2021.102250
Language: English
Additional information: © The Author(s), 2025. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CC-BY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Mrhl, LncRNA, Embryonic stem cells, Transcriptome, Chromatin, Differentiation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/10208291
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