PUBLICATION
The miR-144/Hmgn2 regulatory axis orchestrates chromatin organization during erythropoiesis
- Authors
- Kretov, D.A., Folkes, L., Mora-Martin, A., Walawalkar, I.A., Imrat, ., Syedah, N., Vanuytsel, K., Moxon, S., Murphy, G.J., Cifuentes, D.
- ID
- ZDB-PUB-240508-7
- Date
- 2024
- Source
- Nature communications 15: 38213821 (Journal)
- Registered Authors
- Cifuentes, Daniel
- Keywords
- none
- MeSH Terms
-
- 3' Untranslated Regions/genetics
- Animals
- Cell Differentiation/genetics
- Chromatin*/genetics
- Chromatin*/metabolism
- Erythrocytes/metabolism
- Erythropoiesis*/genetics
- Humans
- Induced Pluripotent Stem Cells/cytology
- Induced Pluripotent Stem Cells/metabolism
- MicroRNAs*/genetics
- MicroRNAs*/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 38714702 Full text @ Nat. Commun.
Citation
Kretov, D.A., Folkes, L., Mora-Martin, A., Walawalkar, I.A., Imrat, ., Syedah, N., Vanuytsel, K., Moxon, S., Murphy, G.J., Cifuentes, D. (2024) The miR-144/Hmgn2 regulatory axis orchestrates chromatin organization during erythropoiesis. Nature communications. 15:38213821.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping