lncRNA LINC00941 modulates MTA2/NuRD occupancy to suppress premature human epidermal differentiation.

Autor:	Morgenstern E; https://ror.org/01eezs655 Regensburg Center for Biochemistry (RCB), University of Regensburg, Regensburg, Germany., Molthof C; https://ror.org/01eezs655 Regensburg Center for Biochemistry (RCB), University of Regensburg, Regensburg, Germany., Schwartz U; https://ror.org/01eezs655 NGS Analysis Center Biology and Pre-Clinical Medicine, University of Regensburg, Regensburg, Germany., Graf J; https://ror.org/01eezs655 Regensburg Center for Biochemistry (RCB), University of Regensburg, Regensburg, Germany., Bruckmann A; https://ror.org/01eezs655 Regensburg Center for Biochemistry (RCB), University of Regensburg, Regensburg, Germany., Hombach S; https://ror.org/01eezs655 Regensburg Center for Biochemistry (RCB), University of Regensburg, Regensburg, Germany.; https://ror.org/006thab72 Institute for Molecular Medicine, MSH Medical School Hamburg, Hamburg, Germany., Kretz M; https://ror.org/01eezs655 Regensburg Center for Biochemistry (RCB), University of Regensburg, Regensburg, Germany markus.kretz@medicalschool-hamburg.de.; https://ror.org/006thab72 Institute for Molecular Medicine, MSH Medical School Hamburg, Hamburg, Germany.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2024 Apr 22; Vol. 7 (7). Date of Electronic Publication: 2024 Apr 22 (Print Publication: 2024).
DOI:	10.26508/lsa.202302475
Abstrakt:	Numerous long non-coding RNAs (lncRNAs) were shown to have a functional impact on cellular processes such as human epidermal homeostasis. However, the mechanism of action for many lncRNAs remains unclear to date. Here, we report that lncRNA LINC00941 regulates keratinocyte differentiation on an epigenetic level through association with the NuRD complex, one of the major chromatin remodelers in cells. We find that LINC00941 interacts with NuRD-associated MTA2 and CHD4 in human primary keratinocytes. LINC00941 perturbation changes MTA2/NuRD occupancy at bivalent chromatin domains in close proximity to transcriptional regulator genes, including the EGR3 gene coding for a transcription factor regulating epidermal differentiation. Notably, LINC00941 depletion resulted in reduced NuRD occupancy at the EGR3 gene locus, increased EGR3 expression in human primary keratinocytes, and increased abundance of EGR3-regulated epidermal differentiation genes in cells and human organotypic epidermal tissues. Our results therefore indicate a role of LINC00941/NuRD in repressing EGR3 expression in non-differentiated keratinocytes, consequentially preventing premature differentiation of human epidermal tissues. (© 2024 Morgenstern et al.)
Databáze:	MEDLINE
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