Sumoylation of the human histone H4 tail inhibits p300-mediated transcription by RNA polymerase II in cellular extracts

The post-translational modification of histones by the small ubiquitin-like modifier (SUMO) protein has been associated with gene regulation, centromeric localization, and double-strand break repair in eukaryotes. Although sumoylation of histone H4 was specifically associated with gene repression, t...

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Autores principales:	Calvin Jon A Leonen, Miho Shimada, Caroline E Weller, Tomoyoshi Nakadai, Peter L Hsu, Elizabeth L Tyson, Arpit Mishra, Patrick MM Shelton, Martin Sadilek, R David Hawkins, Ning Zheng, Robert G Roeder, Champak Chatterjee
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	chromatin histone SUMO acetylation transcription sumoylation Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/30279bf7f3df4f09aea9e207bc1fc733
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spelling	oai:doaj.org-article:30279bf7f3df4f09aea9e207bc1fc7332021-11-26T15:34:39ZSumoylation of the human histone H4 tail inhibits p300-mediated transcription by RNA polymerase II in cellular extracts10.7554/eLife.679522050-084Xe67952https://doaj.org/article/30279bf7f3df4f09aea9e207bc1fc7332021-11-01T00:00:00Zhttps://elifesciences.org/articles/67952https://doaj.org/toc/2050-084XThe post-translational modification of histones by the small ubiquitin-like modifier (SUMO) protein has been associated with gene regulation, centromeric localization, and double-strand break repair in eukaryotes. Although sumoylation of histone H4 was specifically associated with gene repression, this could not be proven due to the challenge of site-specifically sumoylating H4 in cells. Biochemical crosstalk between SUMO and other histone modifications, such as H4 acetylation and H3 methylation, that are associated with active genes also remains unclear. We addressed these challenges in mechanistic studies using an H4 chemically modified at Lys12 by SUMO-3 (H4K12su) and incorporated into mononucleosomes and chromatinized plasmids for functional studies. Mononucleosome-based assays revealed that H4K12su inhibits transcription-activating H4 tail acetylation by the histone acetyltransferase p300, as well as transcription-associated H3K4 methylation by the extended catalytic module of the Set1/COMPASS (complex of proteins associated with Set1) histone methyltransferase complex. Activator- and p300-dependent in vitro transcription assays with chromatinized plasmids revealed that H4K12su inhibits both H4 tail acetylation and RNA polymerase II-mediated transcription. Finally, cell-based assays with a SUMO-H4 fusion that mimics H4 tail sumoylation confirmed the negative crosstalk between histone sumoylation and acetylation/methylation. Thus, our studies establish the key role for histone sumoylation in gene silencing and its negative biochemical crosstalk with active transcription-associated marks in human cells.Calvin Jon A LeonenMiho ShimadaCaroline E WellerTomoyoshi NakadaiPeter L HsuElizabeth L TysonArpit MishraPatrick MM SheltonMartin SadilekR David HawkinsNing ZhengRobert G RoederChampak ChatterjeeeLife Sciences Publications LtdarticlechromatinhistoneSUMOacetylationtranscriptionsumoylationMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chromatin histone SUMO acetylation transcription sumoylation Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	chromatin histone SUMO acetylation transcription sumoylation Medicine R Science Q Biology (General) QH301-705.5 Calvin Jon A Leonen Miho Shimada Caroline E Weller Tomoyoshi Nakadai Peter L Hsu Elizabeth L Tyson Arpit Mishra Patrick MM Shelton Martin Sadilek R David Hawkins Ning Zheng Robert G Roeder Champak Chatterjee Sumoylation of the human histone H4 tail inhibits p300-mediated transcription by RNA polymerase II in cellular extracts
description	The post-translational modification of histones by the small ubiquitin-like modifier (SUMO) protein has been associated with gene regulation, centromeric localization, and double-strand break repair in eukaryotes. Although sumoylation of histone H4 was specifically associated with gene repression, this could not be proven due to the challenge of site-specifically sumoylating H4 in cells. Biochemical crosstalk between SUMO and other histone modifications, such as H4 acetylation and H3 methylation, that are associated with active genes also remains unclear. We addressed these challenges in mechanistic studies using an H4 chemically modified at Lys12 by SUMO-3 (H4K12su) and incorporated into mononucleosomes and chromatinized plasmids for functional studies. Mononucleosome-based assays revealed that H4K12su inhibits transcription-activating H4 tail acetylation by the histone acetyltransferase p300, as well as transcription-associated H3K4 methylation by the extended catalytic module of the Set1/COMPASS (complex of proteins associated with Set1) histone methyltransferase complex. Activator- and p300-dependent in vitro transcription assays with chromatinized plasmids revealed that H4K12su inhibits both H4 tail acetylation and RNA polymerase II-mediated transcription. Finally, cell-based assays with a SUMO-H4 fusion that mimics H4 tail sumoylation confirmed the negative crosstalk between histone sumoylation and acetylation/methylation. Thus, our studies establish the key role for histone sumoylation in gene silencing and its negative biochemical crosstalk with active transcription-associated marks in human cells.
format	article
author	Calvin Jon A Leonen Miho Shimada Caroline E Weller Tomoyoshi Nakadai Peter L Hsu Elizabeth L Tyson Arpit Mishra Patrick MM Shelton Martin Sadilek R David Hawkins Ning Zheng Robert G Roeder Champak Chatterjee
author_facet	Calvin Jon A Leonen Miho Shimada Caroline E Weller Tomoyoshi Nakadai Peter L Hsu Elizabeth L Tyson Arpit Mishra Patrick MM Shelton Martin Sadilek R David Hawkins Ning Zheng Robert G Roeder Champak Chatterjee
author_sort	Calvin Jon A Leonen
title	Sumoylation of the human histone H4 tail inhibits p300-mediated transcription by RNA polymerase II in cellular extracts
title_short	Sumoylation of the human histone H4 tail inhibits p300-mediated transcription by RNA polymerase II in cellular extracts
title_full	Sumoylation of the human histone H4 tail inhibits p300-mediated transcription by RNA polymerase II in cellular extracts
title_fullStr	Sumoylation of the human histone H4 tail inhibits p300-mediated transcription by RNA polymerase II in cellular extracts
title_full_unstemmed	Sumoylation of the human histone H4 tail inhibits p300-mediated transcription by RNA polymerase II in cellular extracts
title_sort	sumoylation of the human histone h4 tail inhibits p300-mediated transcription by rna polymerase ii in cellular extracts
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/30279bf7f3df4f09aea9e207bc1fc733
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Sumoylation of the human histone H4 tail inhibits p300-mediated transcription by RNA polymerase II in cellular extracts

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