The miR-144/Hmgn2 regulatory axis orchestrates chromatin organization during erythropoiesis

Kretov, Dmitry A., Folkes, Leighton, Mora-Martin, Alexandra, Walawalkar, Isha A., Syedah, Imrat Noreen, Vanuytsel, Kim, Moxon, Simon ORCID: https://orcid.org/0000-0003-4644-1816, Murphy, George J. and Cifuentes, Daniel (2024) The miR-144/Hmgn2 regulatory axis orchestrates chromatin organization during erythropoiesis. Nature Communications, 15. ISSN 2041-1723

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Abstract

Differentiation of stem and progenitor cells is a highly regulated process that involves the coordinated action of multiple layers of regulation. Here we show how the post-transcriptional regulatory layer instructs the level of chromatin regulation via miR-144 and its targets to orchestrate chromatin condensation during erythropoiesis. The loss of miR-144 leads to impaired chromatin condensation during erythrocyte maturation. Among the several targets of miR-144 that influence chromatin organization, the miR-144-dependent regulation of Hmgn2 is conserved from fish to humans. Our genetic probing of the miR-144/Hmgn2 regulatory axis established that intact miR-144 target sites in the Hmgn2 3’UTR are necessary for the proper maturation of erythrocytes in both zebrafish and human iPSC-derived erythroid cells while loss of Hmgn2 rescues in part the miR-144 null phenotype. Altogether, our results uncover miR-144 and its target Hmgn2 as the backbone of the genetic regulatory circuit that controls the terminal differentiation of erythrocytes in vertebrates.

Item Type:	Article
Additional Information:	Funding information: This work was supported by the National Institute of Health (US) grant R01GM130935-03 (awarded to D.C.), a seed grant for scRNA-Seq awarded by Boston University Genome Science Institute to D.C. and an RNA-sequencing award awarded by Boston University Genome Science Institute to D.A.K.
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	LivePure Connector
Date Deposited:	23 Apr 2024 13:30
Last Modified:	09 May 2024 13:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/94989
DOI:	10.1101/2023.07.18.549576

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