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 establish 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 |
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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 |
Related URLs: | |
Depositing User: | LivePure Connector |
Date Deposited: | 23 Apr 2024 13:30 |
Last Modified: | 20 May 2024 08:30 |
URI: | https://ueaeprints.uea.ac.uk/id/eprint/94989 |
DOI: | 10.1101/2023.07.18.549576 |
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