| BERESHCHENKO, Oxana, Oriana LO RE, Fedor NIKULENKOV, Sara FLAMINI, Jana KOTAŠKOVÁ, Tommaso MAZZA, Marguerite-Mari LE PANNERER, Marcus BUSCHBECK, Cesarina GIALLONGO, Giuseppe PALUMBO, Giovanni LI VOLTI, Valerio PAZIENZA, Libor ČERVINEK, Carlo RICCARDI, Lumír KREJČÍ, Šárka POSPÍŠILOVÁ, A. Francis STEWART and Manlio VINCIGUERRA. Deficiency and haploinsufficiency of histone macroH2A1.1 in mice recapitulate hematopoietic defects of human myelodysplastic syndrome. CLINICAL EPIGENETICS. LONDON: BMC, 2019, vol. 11, No 1, p. 1-14. ISSN 1868-7075. Available from: https://dx.doi.org/10.1186/s13148-019-0724-z. |
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@article{1604822,
author = {Bereshchenko, Oxana and Lo Re, Oriana and Nikulenkov, Fedor and Flamini, Sara and Kotašková, Jana and Mazza, Tommaso and Le Pannerer, MargueriteandMari and Buschbeck, Marcus and Giallongo, Cesarina and Palumbo, Giuseppe and Li Volti, Giovanni and Pazienza, Valerio and Červinek, Libor and Riccardi, Carlo and Krejčí, Lumír and Pospíšilová, Šárka and Stewart, A. Francis and Vinciguerra, Manlio},
article_location = {LONDON},
article_number = {1},
doi = {http://dx.doi.org/10.1186/s13148-019-0724-z},
keywords = {Hematopoiesis; Myelodysplastic syndrome},
language = {eng},
issn = {1868-7075},
journal = {CLINICAL EPIGENETICS},
title = {Deficiency and haploinsufficiency of histone macroH2A1.1 in mice recapitulate hematopoietic defects of human myelodysplastic syndrome},
url = {https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-019-0724-z},
volume = {11},
year = {2019}
}
TY - JOUR
ID - 1604822
AU - Bereshchenko, Oxana - Lo Re, Oriana - Nikulenkov, Fedor - Flamini, Sara - Kotašková, Jana - Mazza, Tommaso - Le Pannerer, Marguerite-Mari - Buschbeck, Marcus - Giallongo, Cesarina - Palumbo, Giuseppe - Li Volti, Giovanni - Pazienza, Valerio - Červinek, Libor - Riccardi, Carlo - Krejčí, Lumír - Pospíšilová, Šárka - Stewart, A. Francis - Vinciguerra, Manlio
PY - 2019
TI - Deficiency and haploinsufficiency of histone macroH2A1.1 in mice recapitulate hematopoietic defects of human myelodysplastic syndrome
JF - CLINICAL EPIGENETICS
VL - 11
IS - 1
SP - 1-14
EP - 1-14
PB - BMC
SN - 18687075
KW - Hematopoiesis
KW - Myelodysplastic syndrome
UR - https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-019-0724-z
L2 - https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-019-0724-z
N2 - Background Epigenetic 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. Results MacroH2A1.1 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. Conclusions Together, 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.
ER -
BERESHCHENKO, Oxana, Oriana LO RE, Fedor NIKULENKOV, Sara FLAMINI, Jana KOTAŠKOVÁ, Tommaso MAZZA, Marguerite-Mari LE PANNERER, Marcus BUSCHBECK, Cesarina GIALLONGO, Giuseppe PALUMBO, Giovanni LI VOLTI, Valerio PAZIENZA, Libor ČERVINEK, Carlo RICCARDI, Lumír KREJČÍ, Šárka POSPÍŠILOVÁ, A. Francis STEWART and Manlio VINCIGUERRA. Deficiency and haploinsufficiency of histone macroH2A1.1 in mice recapitulate hematopoietic defects of human myelodysplastic syndrome. \textit{CLINICAL EPIGENETICS}. LONDON: BMC, 2019, vol.~11, No~1, p.~1-14. ISSN~1868-7075. Available from: https://dx.doi.org/10.1186/s13148-019-0724-z.
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