GADD45a physically and functionally interacts with TET1

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...

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Main Authors: Kienhöfer, Sabine, Musheev, Michael U., Stapf, Ulrike, Helm, Mark, Schomacher, Lars, Niehrs, Christof, Schäfer, Andrea
Format: Online
Language:English
Published: Elsevier 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673086/
id pubmed-4673086
recordtype oai_dc
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 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/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Kienhöfer, Sabine
Musheev, Michael U.
Stapf, Ulrike
Helm, Mark
Schomacher, Lars
Niehrs, Christof
Schäfer, Andrea
spellingShingle Kienhöfer, Sabine
Musheev, Michael U.
Stapf, Ulrike
Helm, Mark
Schomacher, Lars
Niehrs, Christof
Schäfer, Andrea
GADD45a physically and functionally interacts with TET1
author_facet Kienhöfer, Sabine
Musheev, Michael U.
Stapf, Ulrike
Helm, Mark
Schomacher, Lars
Niehrs, Christof
Schäfer, Andrea
author_sort Kienhöfer, Sabine
title GADD45a physically and functionally interacts with TET1
title_short 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_sort gadd45a physically and functionally interacts with tet1
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.
publisher Elsevier
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673086/
_version_ 1613510806859677696

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