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GADD45a physically and functionally interacts with TET1
DNA demethylation plays a central role during development and in adult physiology. Different mechanisms of active DNA demethylation have been established. For example, Growth Arrest and DNA Damage 45-(GADD45) and Ten-Eleven-Translocation (TET) proteins act in active DNA demethylation but their funct...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673086/ https://www.ncbi.nlm.nih.gov/pubmed/26546041 http://dx.doi.org/10.1016/j.diff.2015.10.003 |
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author | Kienhöfer, Sabine Musheev, Michael U. Stapf, Ulrike Helm, Mark Schomacher, Lars Niehrs, Christof Schäfer, Andrea |
author_facet | Kienhöfer, Sabine Musheev, Michael U. Stapf, Ulrike Helm, Mark Schomacher, Lars Niehrs, Christof Schäfer, Andrea |
author_sort | Kienhöfer, Sabine |
collection | PubMed |
description | DNA demethylation plays a central role during development and in adult physiology. Different mechanisms of active DNA demethylation have been established. For example, Growth Arrest and DNA Damage 45-(GADD45) and Ten-Eleven-Translocation (TET) proteins act in active DNA demethylation but their functional relationship is unresolved. Here we show that GADD45a physically interacts – and functionally cooperates with TET1 in methylcytosine (mC) processing. In reporter demethylation GADD45a requires endogenous TET1 and conversely TET1 requires GADD45a. On GADD45a target genes TET1 hyperinduces 5-hydroxymethylcytosine (hmC) in the presence of GADD45a, while 5-formyl-(fC) and 5-carboxylcytosine (caC) are reduced. Likewise, in global analysis GADD45a positively regulates TET1 mediated mC oxidation and enhances fC/caC removal. Our data suggest a dual function of GADD45a in oxidative DNA demethylation, to promote directly or indirectly TET1 activity and to enhance subsequent fC/caC removal. |
format | Online Article Text |
id | pubmed-4673086 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-46730862015-12-29 GADD45a physically and functionally interacts with TET1 Kienhöfer, Sabine Musheev, Michael U. Stapf, Ulrike Helm, Mark Schomacher, Lars Niehrs, Christof Schäfer, Andrea Differentiation Article DNA demethylation plays a central role during development and in adult physiology. Different mechanisms of active DNA demethylation have been established. For example, Growth Arrest and DNA Damage 45-(GADD45) and Ten-Eleven-Translocation (TET) proteins act in active DNA demethylation but their functional relationship is unresolved. Here we show that GADD45a physically interacts – and functionally cooperates with TET1 in methylcytosine (mC) processing. In reporter demethylation GADD45a requires endogenous TET1 and conversely TET1 requires GADD45a. On GADD45a target genes TET1 hyperinduces 5-hydroxymethylcytosine (hmC) in the presence of GADD45a, while 5-formyl-(fC) and 5-carboxylcytosine (caC) are reduced. Likewise, in global analysis GADD45a positively regulates TET1 mediated mC oxidation and enhances fC/caC removal. Our data suggest a dual function of GADD45a in oxidative DNA demethylation, to promote directly or indirectly TET1 activity and to enhance subsequent fC/caC removal. Elsevier 2015 /pmc/articles/PMC4673086/ /pubmed/26546041 http://dx.doi.org/10.1016/j.diff.2015.10.003 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Kienhöfer, Sabine Musheev, Michael U. Stapf, Ulrike Helm, Mark Schomacher, Lars Niehrs, Christof Schäfer, Andrea GADD45a physically and functionally interacts with TET1 |
title | GADD45a physically and functionally interacts with TET1 |
title_full | GADD45a physically and functionally interacts with TET1 |
title_fullStr | GADD45a physically and functionally interacts with TET1 |
title_full_unstemmed | GADD45a physically and functionally interacts with TET1 |
title_short | GADD45a physically and functionally interacts with TET1 |
title_sort | gadd45a physically and functionally interacts with tet1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673086/ https://www.ncbi.nlm.nih.gov/pubmed/26546041 http://dx.doi.org/10.1016/j.diff.2015.10.003 |
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