ArticleClinical epigenetics2019
Deficiency and haploinsufficiency of histone macroH2A1.1 in mice recapitulate hematopoietic defects of human myelodysplastic syndrome.
Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 30 citations in OpenAlex.
- Histone-based liquid biopsy discriminates between myelodysplastic syndrome and solid malignancies.Clinical epigenetics · 2025Article
- Loss of histone macroH2A1.1 causes kidney abnormalities secondary to a change in nutrient metabolization.Science advances · 2025Article
- Histone variants: key regulators of inflammation in cell dedifferentiation and transdifferentiation.Frontiers in immunology · 2025Review
- The Function of H2A Histone Variants and Their Roles in Diseases.Biomolecules · 2024Review
- Deficiency of histone variant macroH2A1.1 is associated with sexually dimorphic obesity in mice.Scientific reports · 2023Article
- MacroH2A1.1 as a crossroad between epigenetics, inflammation and metabolism of mesenchymal stromal cells in myelodysplastic syndromes.Cell death & disease · 2023Article
- Histone Variants and Their Chaperones in Hematological Malignancies.HemaSphere · 2023Review
- Detection of cell-free histones in the cerebrospinal fluid of pediatric central nervous system malignancies by imaging flow cytometry.Frontiers in molecular biosciences · 2023Article
- Epigenetic remodelling in human hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2022Review
- Histone Variant macroH2A1.1 Enhances Nonhomologous End Joining-dependent DNA Double-strand-break Repair and Reprogramming Efficiency of Human iPSCs.Stem cells (Dayton, Ohio) · 2022Article
- Mutant U2AF1-induced alternative splicing of H2afy (macroH2A1) regulates B-lymphopoiesis in mice.Cell reports · 2021Article
- Cellular senescence or stemness: hypoxia flips the coin.Journal of experimental & clinical cancer research : CR · 2021Review
- The Role of MacroH2A Histone Variants in Cancer.Cancers · 2021Review
- Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment.Cell death & disease · 2021Article
- Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD).Clinical epigenetics · 2020Article
- The taming of PARP1 and its impact on NADMolecular metabolism · 2020Review
- Loss of macroH2A1 decreases mitochondrial metabolism and reduces the aggressiveness of uveal melanoma cells.Aging · 2020Article
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18 authors at 8 institutions in 4 countries.
Funding
Abstract
backgroundEpigenetic regulation is important in hematopoiesis, but the involvement of histone variants is poorly understood. Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic stem cell (HSC) disorders characterized by ineffective hematopoiesis. MacroH2A1.1 is a histone H2A variant that negatively correlates with the self-renewal capacity of embryonic, adult, and cancer stem cells. MacroH2A1.1 is a target of the frequent U2AF1 S34F mutation in MDS. The role of macroH2A1.1 in hematopoiesis is unclear.
resultsMacroH2A1.1 mRNA levels are significantly decreased in patients with low-risk MDS presenting with chromosomal 5q deletion and myeloid cytopenias and tend to be decreased in MDS patients carrying the U2AF1 S34F mutation. Using an innovative mouse allele lacking the macroH2A1.1 alternatively spliced exon, we investigated whether macroH2A1.1 regulates HSC homeostasis and differentiation. The lack of macroH2A1.1 decreased while macroH2A1.1 haploinsufficiency increased HSC frequency upon irradiation. Moreover, bone marrow transplantation experiments showed that both deficiency and haploinsufficiency of macroH2A1.1 resulted in enhanced HSC differentiation along the myeloid lineage. Finally, RNA-sequencing analysis implicated macroH2A1.1-mediated regulation of ribosomal gene expression in HSC homeostasis.
conclusionsTogether, our findings suggest a new epigenetic process contributing to hematopoiesis regulation. By combining clinical data with a discrete mutant mouse model and in vitro studies of human and mouse cells, we identify macroH2A1.1 as a key player in the cellular and molecular features of MDS. These data justify the exploration of macroH2A1.1 and associated proteins as therapeutic targets in hematological malignancies.
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