Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells.
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 h...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3229488?pdf=render |
| _version_ | 1818015802410926080 |
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| author | Eva Bártová Gabriela Šustáčková Lenka Stixová Stanislav Kozubek Soňa Legartová Veronika Foltánková |
| author_facet | Eva Bártová Gabriela Šustáčková Lenka Stixová Stanislav Kozubek Soňa Legartová Veronika Foltánková |
| author_sort | Eva Bártová |
| collection | DOAJ |
| description | 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.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 (γH2AX). Moreover, we observed an ESC-specific nuclear distribution of γH2AX 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.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. |
| first_indexed | 2024-04-14T07:03:34Z |
| format | Article |
| id | doaj.art-599e619380da4effba6a947504c296a5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T07:03:34Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-599e619380da4effba6a947504c296a52022-12-22T02:06:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01612e2728110.1371/journal.pone.0027281Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells.Eva BártováGabriela ŠustáčkováLenka StixováStanislav KozubekSoňa LegartováVeronika FoltánkováOct4 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.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 (γH2AX). Moreover, we observed an ESC-specific nuclear distribution of γH2AX 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.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.http://europepmc.org/articles/PMC3229488?pdf=render |
| spellingShingle | Eva Bártová Gabriela Šustáčková Lenka Stixová Stanislav Kozubek Soňa Legartová Veronika Foltánková Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells. PLoS ONE |
| title | Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells. |
| title_full | Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells. |
| title_fullStr | Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells. |
| title_full_unstemmed | Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells. |
| title_short | Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells. |
| title_sort | recruitment of oct4 protein to uv damaged chromatin in embryonic stem cells |
| url | http://europepmc.org/articles/PMC3229488?pdf=render |
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