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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\u2019UTR 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.<\/jats:p>","DOI":"10.1038\/s41467-024-47982-2","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T12:01:52Z","timestamp":1715083312000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The miR-144\/Hmgn2 regulatory axis orchestrates chromatin organization during erythropoiesis"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1829-8610","authenticated-orcid":false,"given":"Dmitry A.","family":"Kretov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4009-6540","authenticated-orcid":false,"given":"Leighton","family":"Folkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Mora-Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9152-6651","authenticated-orcid":false,"given":"Isha A.","family":"Walawalkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Imrat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noreen","family":"Syedah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8872-0736","authenticated-orcid":false,"given":"Kim","family":"Vanuytsel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4644-1816","authenticated-orcid":false,"given":"Simon","family":"Moxon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3464-793X","authenticated-orcid":false,"given":"George J.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5442-4843","authenticated-orcid":false,"given":"Daniel","family":"Cifuentes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"key":"47982_CR1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.cell.2018.03.006","volume":"173","author":"DP Bartel","year":"2018","unstructured":"Bartel, D. 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