2022
Histone Variant macroH2A1.1 Enhances Nonhomologous End Joining-dependent DNA Double-strand-break Repair and Reprogramming Efficiency of Human iPSCs
GIALLONGO, Sebastiano, Daniela REHAKOVA, Tommaso BIAGINI, Oriana LO RE, Priyanka RAINA et. al.Základní údaje
Originální název
Histone Variant macroH2A1.1 Enhances Nonhomologous End Joining-dependent DNA Double-strand-break Repair and Reprogramming Efficiency of Human iPSCs
Autoři
GIALLONGO, Sebastiano (380 Itálie, domácí), Daniela REHAKOVA (203 Česká republika), Tommaso BIAGINI, Oriana LO RE (380 Itálie), Priyanka RAINA, Gabriela LOCHMANOVÁ (203 Česká republika, domácí), Zbyněk ZDRÁHAL (203 Česká republika, domácí), Igor RESNICK, Pille PATA, Illar PATA, Martin MISTRIK (203 Česká republika), Joao Pedro DE MAGALHAES, Tommaso MAZZA, Irena KOUTNÁ (203 Česká republika, domácí) a Manlio VINCIGUERRA (380 Itálie, garant)
Vydání
Stem Cells, OXFORD, OXFORD UNIV PRESS, 2022, 1066-5099
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
10601 Cell biology
Stát vydavatele
Velká Británie a Severní Irsko
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 5.200
Kód RIV
RIV/00216224:14110/22:00128282
Organizační jednotka
Lékařská fakulta
UT WoS
000765490000005
Klíčová slova anglicky
1; DNA damage; cell reprogramming; induced pluripotent stem cells
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 10. 10. 2024 14:54, Ing. Martina Blahová
Anotace
V originále
DNA damage repair (DDR) is a safeguard for genome integrity maintenance. Increasing DDR efficiency could increase the yield of induced pluripotent stem cells (iPSC) upon reprogramming from somatic cells. The epigenetic mechanisms governing DDR during iPSC reprogramming are not completely understood. Our goal was to evaluate the splicing isoforms of histone variant macroH2A1, macroH2A1.1, and macroH2A1.2, as potential regulators of DDR during iPSC reprogramming. GFP-Trap one-step isolation of mtagGFP-macroH2A1.1 or mtagGFP-macroH2A1.2 fusion proteins from overexpressing human cell lines, followed by liquid chromatography-tandem mass spectrometry analysis, uncovered macroH2A1.1 exclusive interaction with Poly-ADP Ribose Polymerase 1 (PARP1) and X-ray cross-complementing protein 1 (XRCC1). MacroH2A1.1 overexpression in U2OS-GFP reporter cells enhanced specifically nonhomologous end joining (NHEJ) repair pathway, while macroH2A1.1 knock-out (KO) mice showed an impaired DDR capacity. The exclusive interaction of macroH2A1.1, but not macroH2A1.2, with PARP1/XRCC1, was confirmed in human umbilical vein endothelial cells (HUVEC) undergoing reprogramming into iPSC through episomal vectors. In HUVEC, macroH2A1.1 overexpression activated transcriptional programs that enhanced DDR and reprogramming. Consistently, macroH2A1.1 but not macroH2A1.2 overexpression improved iPSC reprogramming. We propose the macroH2A1 splicing isoform macroH2A1.1 as a promising epigenetic target to improve iPSC genome stability and therapeutic potential.
Návaznosti
GF19-29701L, projekt VaV |
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LM2018127, projekt VaV |
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90127, velká výzkumná infrastruktura |
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