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

Dmitry A. Kretov, Leighton Folkes, Alexandra Mora-Martin, Isha A. Walawalkar, Imrat, Noreen Syedah, Kim Vanuytsel, Simon Moxon, George J. Murphy and Daniel Cifuentes ()
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Dmitry A. Kretov: Boston University Chobanian & Avedisian School of Medicine
Leighton Folkes: University of East Anglia
Alexandra Mora-Martin: Boston University Chobanian & Avedisian School of Medicine
Isha A. Walawalkar: Boston University Chobanian & Avedisian School of Medicine
Imrat: Boston University Chobanian & Avedisian School of Medicine
Noreen Syedah: Boston University Chobanian & Avedisian School of Medicine
Kim Vanuytsel: Boston University Chobanian & Avedisian School of Medicine
Simon Moxon: University of East Anglia
George J. Murphy: Boston University Chobanian & Avedisian School of Medicine
Daniel Cifuentes: Boston University Chobanian & Avedisian School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47982-2

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