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Set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity

Methylation of histone H3 lysine 36 (H3K36me) by yeast Set2 is critical for the maintenance of chromatin structure and transcriptional fidelity. However, we do not know the full range of Set2/H3K36me functions or the scope of mechanisms that regulate Set2-dependent H3K36 methylation. Here, we show t...

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Autores principales: Dronamraju, Raghuvar, Jha, Deepak Kumar, Eser, Umut, Adams, Alexander T, Dominguez, Daniel, Choudhury, Rajarshi, Chiang, Yun-Chen, Rathmell, W Kimryn, Emanuele, Michael J, Churchman, L Stirling, Strahl, Brian D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814799/
https://www.ncbi.nlm.nih.gov/pubmed/29294086
http://dx.doi.org/10.1093/nar/gkx1276
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author Dronamraju, Raghuvar
Jha, Deepak Kumar
Eser, Umut
Adams, Alexander T
Dominguez, Daniel
Choudhury, Rajarshi
Chiang, Yun-Chen
Rathmell, W Kimryn
Emanuele, Michael J
Churchman, L Stirling
Strahl, Brian D
author_facet Dronamraju, Raghuvar
Jha, Deepak Kumar
Eser, Umut
Adams, Alexander T
Dominguez, Daniel
Choudhury, Rajarshi
Chiang, Yun-Chen
Rathmell, W Kimryn
Emanuele, Michael J
Churchman, L Stirling
Strahl, Brian D
author_sort Dronamraju, Raghuvar
collection PubMed
description Methylation of histone H3 lysine 36 (H3K36me) by yeast Set2 is critical for the maintenance of chromatin structure and transcriptional fidelity. However, we do not know the full range of Set2/H3K36me functions or the scope of mechanisms that regulate Set2-dependent H3K36 methylation. Here, we show that the APC/C(CDC20) complex regulates Set2 protein abundance during the cell cycle. Significantly, absence of Set2-mediated H3K36me causes a loss of cell cycle control and pronounced defects in the transcriptional fidelity of cell cycle regulatory genes, a class of genes that are generally long, hence highly dependent on Set2/H3K36me for their transcriptional fidelity. Because APC/C also controls human SETD2, and SETD2 likewise regulates cell cycle progression, our data imply an evolutionarily conserved cell cycle function for Set2/SETD2 that may explain why recurrent mutations of SETD2 contribute to human disease.
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spelling pubmed-58147992018-02-23 Set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity Dronamraju, Raghuvar Jha, Deepak Kumar Eser, Umut Adams, Alexander T Dominguez, Daniel Choudhury, Rajarshi Chiang, Yun-Chen Rathmell, W Kimryn Emanuele, Michael J Churchman, L Stirling Strahl, Brian D Nucleic Acids Res Molecular Biology Methylation of histone H3 lysine 36 (H3K36me) by yeast Set2 is critical for the maintenance of chromatin structure and transcriptional fidelity. However, we do not know the full range of Set2/H3K36me functions or the scope of mechanisms that regulate Set2-dependent H3K36 methylation. Here, we show that the APC/C(CDC20) complex regulates Set2 protein abundance during the cell cycle. Significantly, absence of Set2-mediated H3K36me causes a loss of cell cycle control and pronounced defects in the transcriptional fidelity of cell cycle regulatory genes, a class of genes that are generally long, hence highly dependent on Set2/H3K36me for their transcriptional fidelity. Because APC/C also controls human SETD2, and SETD2 likewise regulates cell cycle progression, our data imply an evolutionarily conserved cell cycle function for Set2/SETD2 that may explain why recurrent mutations of SETD2 contribute to human disease. Oxford University Press 2018-02-16 2017-12-23 /pmc/articles/PMC5814799/ /pubmed/29294086 http://dx.doi.org/10.1093/nar/gkx1276 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Molecular Biology
Dronamraju, Raghuvar
Jha, Deepak Kumar
Eser, Umut
Adams, Alexander T
Dominguez, Daniel
Choudhury, Rajarshi
Chiang, Yun-Chen
Rathmell, W Kimryn
Emanuele, Michael J
Churchman, L Stirling
Strahl, Brian D
Set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity
title Set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity
title_full Set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity
title_fullStr Set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity
title_full_unstemmed Set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity
title_short Set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity
title_sort set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814799/
https://www.ncbi.nlm.nih.gov/pubmed/29294086
http://dx.doi.org/10.1093/nar/gkx1276
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