Recruitment of Oct4 protein to UV-damaged chromatin in
embryonic stem cells.

J 2011

Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells.

BÁRTOVÁ, Eva; Gabriela ŠUSTÁČKOVÁ; Lenka STIXOVÁ; Stanislav KOZUBEK; Soňa LEGARTOVÁ et al.

Základní údaje

Originální název

Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells.

Autoři

BÁRTOVÁ, Eva; Gabriela ŠUSTÁČKOVÁ; Lenka STIXOVÁ; Stanislav KOZUBEK; Soňa LEGARTOVÁ a Veronika FOLTÁNKOVÁ

Vydání

PloS ONE, 2011, 1932-6203

Další údaje

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.092

Označené pro přenos do RIV

DOI

https://doi.org/10.1371/journal.pone.0027281

UT WoS

000298171400008

Klíčová slova anglicky

DOUBLE-STRAND BREAKS; HISTONE H2AX PHOSPHORYLATION; DNA-DAMAGE; ES CELLS; HETEROCHROMATIN PROTEIN-1; GENE-EXPRESSION; POU DOMAIN; DIFFERENTIATION; REPAIR; NANOG

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 12. 7. 2012 10:12, Mgr. Veronika Janečková, Ph.D.

Anotace

V originále

BACKGROUND: Oct4 is a specific marker of embryonic stem cell (ESC) pluripotency. However, little is known regarding how Oct4 responds to DNA damage. Here, we investigated whether Oct4 recognizes damaged chromatin in mouse ESCs stably expressing GFP-Oct4. These experiments should contribute to the knowledge of how ESC genomic integrity is maintained, which is crucial for potential application of human ESCs in regenerative medicine. METHODOLOGY/PRINCIPAL FINDINGS: We used time-lapse confocal microscopy, microirradiation by UV laser (355 nm), induction of DNA lesions by specific agents, and GFP technology to study the Oct4 response to DNA damage. We found that Oct4 accumulates in UV-damaged regions immediately after irradiation in an adenosine triphosphate-dependent manner. Intriguingly, this event was not accompanied by pronounced Nanog and c-MYC recruitment to the UV-damaged sites. The accumulation of Oct4 to UV-damaged chromatin occurred simultaneously with H3K9 deacetylation and H2AX phosphorylation (gammaH2AX). Moreover, we observed an ESC-specific nuclear distribution of gammaH2AX after interference to cellular processes, including histone acetylation, transcription, and cell metabolism. Inhibition of histone deacetylases mostly prevented pronounced Oct4 accumulation at UV-irradiated chromatin. CONCLUSIONS/SIGNIFICANCE: Our studies demonstrate pluripotency-specific events that accompany DNA damage responses. Here, we discuss how ESCs might respond to DNA damage caused by genotoxic injury that might lead to unwanted genomic instability.

Citovat

BÁRTOVÁ, Eva; Gabriela ŠUSTÁČKOVÁ; Lenka STIXOVÁ; Stanislav KOZUBEK; Soňa LEGARTOVÁ a Veronika FOLTÁNKOVÁ. Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells. PloS ONE. 2011, roč. 2011, č. 6, s. e27281. ISSN 1932-6203. Dostupné z: https://doi.org/10.1371/journal.pone.0027281.

@article{986878,
   author = {Bártová, Eva and Šustáčková, Gabriela and Stixová, Lenka and Kozubek, Stanislav and Legartová, Soňa and Foltánková, Veronika},
   article_number = {6},
   doi = {https://doi.org/10.1371/journal.pone.0027281},
   keywords = {DOUBLE-STRAND BREAKS; HISTONE H2AX PHOSPHORYLATION; DNA-DAMAGE; ES CELLS; HETEROCHROMATIN PROTEIN-1; GENE-EXPRESSION; POU DOMAIN; DIFFERENTIATION; REPAIR; NANOG},
   issn = {1932-6203},
   journal = {PloS ONE},
   title = {Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells.},
   url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229488/?tool=pubmed},
   volume = {2011},
   year = {2011}
}

TY  - JOUR
ID  - 986878
AU  - Bártová, Eva - Šustáčková, Gabriela - Stixová, Lenka - Kozubek, Stanislav - Legartová, Soňa - Foltánková, Veronika
PY  - 2011
TI  - Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells.
JF  - PloS ONE
VL  - 2011
IS  - 6
SP  - e27281
EP  - e27281
SN  - 19326203
KW  - DOUBLE-STRAND BREAKS
KW  - HISTONE H2AX PHOSPHORYLATION
KW  - DNA-DAMAGE
KW  - ES CELLS
KW  - HETEROCHROMATIN PROTEIN-1
KW  - GENE-EXPRESSION
KW  - POU DOMAIN
KW  - DIFFERENTIATION
KW  - REPAIR
KW  - NANOG
UR  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229488/?tool=pubmed
L2  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229488/?tool=pubmed
N2  - BACKGROUND: Oct4 is a specific marker of embryonic stem cell (ESC) pluripotency. However, little is known regarding how Oct4 responds to DNA damage. Here, we investigated whether Oct4 recognizes damaged chromatin in mouse ESCs stably expressing GFP-Oct4. These experiments should contribute to the knowledge of how ESC genomic integrity is maintained, which is crucial for potential application of human ESCs in regenerative medicine. METHODOLOGY/PRINCIPAL FINDINGS: We used time-lapse confocal microscopy, microirradiation by UV laser (355 nm), induction of DNA lesions by specific agents, and GFP technology to study the Oct4 response to DNA damage. We found that Oct4 accumulates in UV-damaged regions immediately after irradiation in an adenosine triphosphate-dependent manner. Intriguingly, this event was not accompanied by pronounced Nanog and c-MYC recruitment to the UV-damaged sites. The accumulation of Oct4 to UV-damaged chromatin occurred simultaneously with H3K9 deacetylation and H2AX phosphorylation (gammaH2AX). Moreover, we observed an ESC-specific nuclear distribution of gammaH2AX after interference to cellular processes, including histone acetylation, transcription, and cell metabolism. Inhibition of histone deacetylases mostly prevented pronounced Oct4 accumulation at UV-irradiated chromatin. CONCLUSIONS/SIGNIFICANCE: Our studies demonstrate pluripotency-specific events that accompany DNA damage responses. Here, we discuss how ESCs might respond to DNA damage caused by genotoxic injury that might lead to unwanted genomic instability.
ER  -

BÁRTOVÁ, Eva; Gabriela ŠUSTÁČKOVÁ; Lenka STIXOVÁ; Stanislav KOZUBEK; Soňa LEGARTOVÁ a Veronika FOLTÁNKOVÁ. Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells. \textit{PloS ONE}. 2011, roč.~2011, č.~6, s.~e27281. ISSN~1932-6203. Dostupné z: https://doi.org/10.1371/journal.pone.0027281.

Přehled o publikaci