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, Daniel Cifuentes (Lead Author)

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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.

Original languageEnglish
Article number3821
JournalNature Communications
Publication statusPublished - 7 May 2024

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