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)

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number3821
JournalNature Communications
Volume15
DOIs
Publication statusPublished - 7 May 2024

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