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Balancing acts of SRI and an auto-inhibitory domain specify Set2 function at transcribed chromatin

Set2-mediated H3K36 methylation ubiquitously functions in coding regions in all eukaryotes. It has been linked to the regulation of acetylation states, histone exchange, alternative splicing, DNA repair and recombination. Set2 is recruited to transcribed chromatin through its SRI domain's direc...

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Autores principales: Wang, Yi, Niu, Yanling, Li, Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446442/
https://www.ncbi.nlm.nih.gov/pubmed/25925577
http://dx.doi.org/10.1093/nar/gkv393
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author Wang, Yi
Niu, Yanling
Li, Bing
author_facet Wang, Yi
Niu, Yanling
Li, Bing
author_sort Wang, Yi
collection PubMed
description Set2-mediated H3K36 methylation ubiquitously functions in coding regions in all eukaryotes. It has been linked to the regulation of acetylation states, histone exchange, alternative splicing, DNA repair and recombination. Set2 is recruited to transcribed chromatin through its SRI domain's direct association with phosphorylated Pol II. However, regulatory mechanisms for histone modifying enzymes like Set2 that travel with elongating Pol II remain largely unknown beyond their initial recruitment events. Here, by fusing Set2 to RNA Pol II, we found that the SRI domain can also recognize linker DNA of chromatin, thereby controlling Set2 substrate specificity. We also discovered that an auto-inhibitory domain (AID) of Set2 primarily restricts Set2 activity to transcribed chromatin and fine-tunes several functions of SRI. Finally, we demonstrated that AID mutations caused hyperactive Set2 in vivo and displayed a synthetic interaction with the histone chaperone FACT. Our data suggest that Set2 is intrinsically regulated through multiple mechanisms and emphasize the importance of a precise temporal control of H3K36 methylation during the dynamic transcription elongation process.
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spelling pubmed-44464422015-06-15 Balancing acts of SRI and an auto-inhibitory domain specify Set2 function at transcribed chromatin Wang, Yi Niu, Yanling Li, Bing Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Set2-mediated H3K36 methylation ubiquitously functions in coding regions in all eukaryotes. It has been linked to the regulation of acetylation states, histone exchange, alternative splicing, DNA repair and recombination. Set2 is recruited to transcribed chromatin through its SRI domain's direct association with phosphorylated Pol II. However, regulatory mechanisms for histone modifying enzymes like Set2 that travel with elongating Pol II remain largely unknown beyond their initial recruitment events. Here, by fusing Set2 to RNA Pol II, we found that the SRI domain can also recognize linker DNA of chromatin, thereby controlling Set2 substrate specificity. We also discovered that an auto-inhibitory domain (AID) of Set2 primarily restricts Set2 activity to transcribed chromatin and fine-tunes several functions of SRI. Finally, we demonstrated that AID mutations caused hyperactive Set2 in vivo and displayed a synthetic interaction with the histone chaperone FACT. Our data suggest that Set2 is intrinsically regulated through multiple mechanisms and emphasize the importance of a precise temporal control of H3K36 methylation during the dynamic transcription elongation process. Oxford University Press 2015-05-26 2015-04-29 /pmc/articles/PMC4446442/ /pubmed/25925577 http://dx.doi.org/10.1093/nar/gkv393 Text en © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene regulation, Chromatin and Epigenetics
Wang, Yi
Niu, Yanling
Li, Bing
Balancing acts of SRI and an auto-inhibitory domain specify Set2 function at transcribed chromatin
title Balancing acts of SRI and an auto-inhibitory domain specify Set2 function at transcribed chromatin
title_full Balancing acts of SRI and an auto-inhibitory domain specify Set2 function at transcribed chromatin
title_fullStr Balancing acts of SRI and an auto-inhibitory domain specify Set2 function at transcribed chromatin
title_full_unstemmed Balancing acts of SRI and an auto-inhibitory domain specify Set2 function at transcribed chromatin
title_short Balancing acts of SRI and an auto-inhibitory domain specify Set2 function at transcribed chromatin
title_sort balancing acts of sri and an auto-inhibitory domain specify set2 function at transcribed chromatin
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446442/
https://www.ncbi.nlm.nih.gov/pubmed/25925577
http://dx.doi.org/10.1093/nar/gkv393
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