Histone Variant macroH2A1.1 Enhances Nonhomologous End
Joining-dependent DNA Double-strand-break Repair and
Reprogramming Efficiency of Human iPSCs

J 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.

Basic information

Original name

Histone Variant macroH2A1.1 Enhances Nonhomologous End Joining-dependent DNA Double-strand-break Repair and Reprogramming Efficiency of Human iPSCs

Authors

GIALLONGO, Sebastiano (380 Italy, belonging to the institution), Daniela REHAKOVA (203 Czech Republic), Tommaso BIAGINI, Oriana LO RE (380 Italy), Priyanka RAINA, Gabriela LOCHMANOVÁ (203 Czech Republic, belonging to the institution), Zbyněk ZDRÁHAL (203 Czech Republic, belonging to the institution), Igor RESNICK, Pille PATA, Illar PATA, Martin MISTRIK (203 Czech Republic), Joao Pedro DE MAGALHAES, Tommaso MAZZA, Irena KOUTNÁ (203 Czech Republic, belonging to the institution) and Manlio VINCIGUERRA (380 Italy, guarantor)

Edition

Stem Cells, OXFORD, OXFORD UNIV PRESS, 2022, 1066-5099

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.200

RIV identification code

RIV/00216224:14110/22:00128282

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1093/stmcls/sxab004

UT WoS

000765490000005

Keywords in English

1; DNA damage; cell reprogramming; induced pluripotent stem cells

Abstract

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.

Links

GF19-29701L, research and development project

Name: Funkce HDAC1 v T-buněčných lymfomech

Investor: Czech Science Foundation, Partner Agency (Austria)

LM2018127, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR

90127, large research infrastructures

Name: CIISB II

Citovat

GIALLONGO, Sebastiano, Daniela REHAKOVA, Tommaso BIAGINI, Oriana LO RE, Priyanka RAINA, Gabriela LOCHMANOVÁ, Zbyněk ZDRÁHAL, Igor RESNICK, Pille PATA, Illar PATA, Martin MISTRIK, Joao Pedro DE MAGALHAES, Tommaso MAZZA, Irena KOUTNÁ and Manlio VINCIGUERRA. Histone Variant macroH2A1.1 Enhances Nonhomologous End Joining-dependent DNA Double-strand-break Repair and Reprogramming Efficiency of Human iPSCs. Stem Cells. OXFORD: OXFORD UNIV PRESS, 2022, vol. 40, No 1, p. 35-48. ISSN 1066-5099. Available from: https://dx.doi.org/10.1093/stmcls/sxab004.

@article{2249639,
   author = {Giallongo, Sebastiano and Rehakova, Daniela and Biagini, Tommaso and Lo Re, Oriana and Raina, Priyanka and Lochmanová, Gabriela and Zdráhal, Zbyněk and Resnick, Igor and Pata, Pille and Pata, Illar and Mistrik, Martin and de Magalhaes, Joao Pedro and Mazza, Tommaso and Koutná, Irena and Vinciguerra, Manlio},
   article_location = {OXFORD},
   article_number = {1},
   doi = {http://dx.doi.org/10.1093/stmcls/sxab004},
   keywords = {1; DNA damage; cell reprogramming; induced pluripotent stem cells},
   language = {eng},
   issn = {1066-5099},
   journal = {Stem Cells},
   note = {Korespondenční autor nereagoval na žádost o doplnění podílu. Podíl doplněn rovnocenně podle počtu participujících HS (dle rozhodnutí vedení PřF).},
   title = {Histone Variant macroH2A1.1 Enhances Nonhomologous End Joining-dependent DNA Double-strand-break Repair and Reprogramming Efficiency of Human iPSCs},
   url = {https://academic.oup.com/stmcls/article/40/1/35/6511687?login=true},
   volume = {40},
   year = {2022}
}

TY  - JOUR
ID  - 2249639
AU  - Giallongo, Sebastiano - Rehakova, Daniela - Biagini, Tommaso - Lo Re, Oriana - Raina, Priyanka - Lochmanová, Gabriela - Zdráhal, Zbyněk - Resnick, Igor - Pata, Pille - Pata, Illar - Mistrik, Martin - de Magalhaes, Joao Pedro - Mazza, Tommaso - Koutná, Irena - Vinciguerra, Manlio
PY  - 2022
TI  - Histone Variant macroH2A1.1 Enhances Nonhomologous End Joining-dependent DNA Double-strand-break Repair and Reprogramming Efficiency of Human iPSCs
JF  - Stem Cells
VL  - 40
IS  - 1
SP  - 35-48
EP  - 35-48
PB  - OXFORD UNIV PRESS
SN  - 10665099
N1  - Korespondenční autor nereagoval na žádost o doplnění podílu. Podíl doplněn rovnocenně podle počtu participujících HS (dle rozhodnutí vedení PřF).
KW  - 1
KW  - DNA damage
KW  - cell reprogramming
KW  - induced pluripotent stem cells
UR  - https://academic.oup.com/stmcls/article/40/1/35/6511687?login=true
N2  - 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.
ER  -

GIALLONGO, Sebastiano, Daniela REHAKOVA, Tommaso BIAGINI, Oriana LO RE, Priyanka RAINA, Gabriela LOCHMANOVÁ, Zbyněk ZDRÁHAL, Igor RESNICK, Pille PATA, Illar PATA, Martin MISTRIK, Joao Pedro DE MAGALHAES, Tommaso MAZZA, Irena KOUTNÁ and Manlio VINCIGUERRA. Histone Variant macroH2A1.1 Enhances Nonhomologous End Joining-dependent DNA Double-strand-break Repair and Reprogramming Efficiency of Human iPSCs. \textit{Stem Cells}. OXFORD: OXFORD UNIV PRESS, 2022, vol.~40, No~1, p.~35-48. ISSN~1066-5099. Available from: https://dx.doi.org/10.1093/stmcls/sxab004.

Detailed Information on Publication Record