Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

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

S. Giallongo, D. Řeháková, T. Biagini, O. Lo Re, P. Raina, G. Lochmanová, Z. Zdráhal, I. Resnick, P. Pata, I. Pata, M. Mistrík, JP. de Magalhães, T. Mazza, I. Koutná, M. Vinciguerra

. 2022 ; 40 (1) : 35-48. [pub] 20220303

Jazyk angličtina Země Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc22019233

Grantová podpora
208375/Z/17/Z Wellcome Trust - United Kingdom

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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22019233
003      
CZ-PrNML
005      
20220804135444.0
007      
ta
008      
220720s2022 xxk f 000 0|eng||
009      
AR
024    7_
$a 10.1093/stmcls/sxab004 $2 doi
035    __
$a (PubMed)35511867
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxk
100    1_
$a Giallongo, Sebastiano $u International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic $u Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
245    10
$a Histone Variant macroH2A1.1 Enhances Nonhomologous End Joining-dependent DNA Double-strand-break Repair and Reprogramming Efficiency of Human iPSCs / $c S. Giallongo, D. Řeháková, T. Biagini, O. Lo Re, P. Raina, G. Lochmanová, Z. Zdráhal, I. Resnick, P. Pata, I. Pata, M. Mistrík, JP. de Magalhães, T. Mazza, I. Koutná, M. Vinciguerra
520    9_
$a 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.
650    _2
$a zvířata $7 D000818
650    _2
$a DNA $7 D004247
650    _2
$a oprava DNA $7 D004260
650    _2
$a endoteliální buňky $x metabolismus $7 D042783
650    12
$a histony $x metabolismus $7 D006657
650    _2
$a lidé $7 D006801
650    12
$a indukované pluripotentní kmenové buňky $x metabolismus $7 D057026
650    _2
$a myši $7 D051379
650    _2
$a protein XRCC1 $x genetika $x metabolismus $7 D000076105
655    _2
$a časopisecké články $7 D016428
700    1_
$a Řeháková, Daniela $u International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic
700    1_
$a Biagini, Tommaso $u Laboratory of Bioinformatics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
700    1_
$a Lo Re, Oriana $u International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic $u Department of Translational Stem Cell Biology, Research Institute of the Medical University of Varna (RIMUV), Varna, Bulgaria
700    1_
$a Raina, Priyanka $u Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK
700    1_
$a Lochmanová, Gabriela $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic
700    1_
$a Zdráhal, Zbyněk $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic $u National Centre for Biomolecular Research, Masaryk University, Brno, Czech Republic
700    1_
$a Resnick, Igor $u Department of Translational Stem Cell Biology, Research Institute of the Medical University of Varna (RIMUV), Varna, Bulgaria $u Program for Hematology, Immunology, BMT and Cell therapy, St. Marina University Hospital, Varna, Bulgaria $u Department of Medical Genetics, Medical University of Varna, Varna, Bulgaria
700    1_
$a Pata, Pille $u Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia $u IVEX Lab, Akadeemia 15, Tallinn, Estonia
700    1_
$a Pata, Illar $u Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia
700    1_
$a Mistrík, Martin $u Laboratory of Genome Integrity, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
700    1_
$a de Magalhães, João Pedro $u Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK
700    1_
$a Mazza, Tommaso $u Department of Translational Stem Cell Biology, Research Institute of the Medical University of Varna (RIMUV), Varna, Bulgaria
700    1_
$a Koutná, Irena $u International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic $u Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
700    1_
$a Vinciguerra, Manlio $u International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic $u Department of Translational Stem Cell Biology, Research Institute of the Medical University of Varna (RIMUV), Varna, Bulgaria
773    0_
$w MED00004436 $t Stem cells (Dayton, Ohio) $x 1549-4918 $g Roč. 40, č. 1 (2022), s. 35-48
856    41
$u https://pubmed.ncbi.nlm.nih.gov/35511867 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20220720 $b ABA008
991    __
$a 20220804135438 $b ABA008
999    __
$a ok $b bmc $g 1822713 $s 1170476
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2022 $b 40 $c 1 $d 35-48 $e 20220303 $i 1549-4918 $m Stem cells $n Stem Cells $x MED00004436
GRA    __
$a 208375/Z/17/Z $p Wellcome Trust $2 United Kingdom
LZP    __
$a Pubmed-20220720

Najít záznam

Citační ukazatele

Možnosti archivace