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bioRxiv · 10.1101/2023.07.18.549576

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

Kretov, D.·Folkes, L.·Mora-Martin, A.·Syedah, N.·Walawalkar, I. A.·Vanuytsel, K.·Murphy, G. J.·Moxon, S.·Cifuentes, D.
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Abstract

SUMMARYDifferentiation 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 3UTR 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.

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Kretov, D., Folkes, L., Mora-Martin, A., Syedah, N., Walawalkar, I. A., Vanuytsel, K., Murphy, G. J., Moxon, S., Cifuentes, D.. 2023-07-19. The miR-144/Hmgn2 regulatory axis orchestrates chromatin organization during erythropoiesis. https://doi.org/10.1101/2023.07.18.549576

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