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Nat Commun ; 15(1): 3821, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714702

RESUMO

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.


Assuntos
Cromatina , Eritropoese , MicroRNAs , Peixe-Zebra , MicroRNAs/metabolismo , MicroRNAs/genética , Eritropoese/genética , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Humanos , Animais , Cromatina/metabolismo , Cromatina/genética , Eritrócitos/metabolismo , Regiões 3' não Traduzidas/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Diferenciação Celular/genética
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