Protein complex interactor analysis and differential activity of KDM3 subfamily members towards H3K9 methylation.

Histone modifications play an important role in chromatin organization and gene regulation, and their interpretation is referred to as epigenetic control. The methylation levels of several lysine residues in histone tails are tightly controlled, and JmjC domain-containing proteins are one class of b...

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Autores principales:	Michael Brauchle, Zhiping Yao, Rishi Arora, Sachin Thigale, Ieuan Clay, Bruno Inverardi, Joy Fletcher, Paul Taslimi, Michael G Acker, Bertran Gerrits, Johannes Voshol, Andreas Bauer, Dirk Schübeler, Tewis Bouwmeester, Heinz Ruffner
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1a29280cc2c64abea83155ffa4d309fa
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spelling	oai:doaj.org-article:1a29280cc2c64abea83155ffa4d309fa2021-11-18T07:49:47ZProtein complex interactor analysis and differential activity of KDM3 subfamily members towards H3K9 methylation.1932-620310.1371/journal.pone.0060549https://doaj.org/article/1a29280cc2c64abea83155ffa4d309fa2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23593242/?tool=EBIhttps://doaj.org/toc/1932-6203Histone modifications play an important role in chromatin organization and gene regulation, and their interpretation is referred to as epigenetic control. The methylation levels of several lysine residues in histone tails are tightly controlled, and JmjC domain-containing proteins are one class of broadly expressed enzymes catalyzing methyl group removal. However, several JmjC proteins remain uncharacterized, gaps persist in understanding substrate recognition, and the integration of JmjC proteins into signaling pathways is just emerging. The KDM3 subfamily is an evolutionarily conserved group of histone demethylase proteins, thought to share lysine substrate specificity. Here we use a systematic approach to compare KDM3 subfamily members. We show that full-length KDM3A and KDM3B are H3K9me1/2 histone demethylases whereas we fail to observe histone demethylase activity for JMJD1C using immunocytochemical and biochemical approaches. Structure-function analyses revealed the importance of a single amino acid in KDM3A implicated in the catalytic activity towards H3K9me1/2 that is not conserved in JMJD1C. Moreover, we use quantitative proteomic analyses to identify subsets of the interactomes of the 3 proteins. Specific interactor candidates were identified for each of the three KDM3 subfamily members. Importantly, we find that SCAI, a known transcriptional repressor, interacts specifically with KDM3B. Taken together, we identify substantial differences in the biology of KDM3 histone demethylases, namely enzymatic activity and protein-protein interactions. Such comparative approaches pave the way to a better understanding of histone demethylase specificity and protein function at a systems level and are instrumental in identifying the more subtle differences between closely related proteins.Michael BrauchleZhiping YaoRishi AroraSachin ThigaleIeuan ClayBruno InverardiJoy FletcherPaul TaslimiMichael G AckerBertran GerritsJohannes VosholAndreas BauerDirk SchübelerTewis BouwmeesterHeinz RuffnerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e60549 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michael Brauchle Zhiping Yao Rishi Arora Sachin Thigale Ieuan Clay Bruno Inverardi Joy Fletcher Paul Taslimi Michael G Acker Bertran Gerrits Johannes Voshol Andreas Bauer Dirk Schübeler Tewis Bouwmeester Heinz Ruffner Protein complex interactor analysis and differential activity of KDM3 subfamily members towards H3K9 methylation.
description	Histone modifications play an important role in chromatin organization and gene regulation, and their interpretation is referred to as epigenetic control. The methylation levels of several lysine residues in histone tails are tightly controlled, and JmjC domain-containing proteins are one class of broadly expressed enzymes catalyzing methyl group removal. However, several JmjC proteins remain uncharacterized, gaps persist in understanding substrate recognition, and the integration of JmjC proteins into signaling pathways is just emerging. The KDM3 subfamily is an evolutionarily conserved group of histone demethylase proteins, thought to share lysine substrate specificity. Here we use a systematic approach to compare KDM3 subfamily members. We show that full-length KDM3A and KDM3B are H3K9me1/2 histone demethylases whereas we fail to observe histone demethylase activity for JMJD1C using immunocytochemical and biochemical approaches. Structure-function analyses revealed the importance of a single amino acid in KDM3A implicated in the catalytic activity towards H3K9me1/2 that is not conserved in JMJD1C. Moreover, we use quantitative proteomic analyses to identify subsets of the interactomes of the 3 proteins. Specific interactor candidates were identified for each of the three KDM3 subfamily members. Importantly, we find that SCAI, a known transcriptional repressor, interacts specifically with KDM3B. Taken together, we identify substantial differences in the biology of KDM3 histone demethylases, namely enzymatic activity and protein-protein interactions. Such comparative approaches pave the way to a better understanding of histone demethylase specificity and protein function at a systems level and are instrumental in identifying the more subtle differences between closely related proteins.
format	article
author	Michael Brauchle Zhiping Yao Rishi Arora Sachin Thigale Ieuan Clay Bruno Inverardi Joy Fletcher Paul Taslimi Michael G Acker Bertran Gerrits Johannes Voshol Andreas Bauer Dirk Schübeler Tewis Bouwmeester Heinz Ruffner
author_facet	Michael Brauchle Zhiping Yao Rishi Arora Sachin Thigale Ieuan Clay Bruno Inverardi Joy Fletcher Paul Taslimi Michael G Acker Bertran Gerrits Johannes Voshol Andreas Bauer Dirk Schübeler Tewis Bouwmeester Heinz Ruffner
author_sort	Michael Brauchle
title	Protein complex interactor analysis and differential activity of KDM3 subfamily members towards H3K9 methylation.
title_short	Protein complex interactor analysis and differential activity of KDM3 subfamily members towards H3K9 methylation.
title_full	Protein complex interactor analysis and differential activity of KDM3 subfamily members towards H3K9 methylation.
title_fullStr	Protein complex interactor analysis and differential activity of KDM3 subfamily members towards H3K9 methylation.
title_full_unstemmed	Protein complex interactor analysis and differential activity of KDM3 subfamily members towards H3K9 methylation.
title_sort	protein complex interactor analysis and differential activity of kdm3 subfamily members towards h3k9 methylation.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/1a29280cc2c64abea83155ffa4d309fa
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Protein complex interactor analysis and differential activity of KDM3 subfamily members towards H3K9 methylation.

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