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Positive cofactor 4 (PC4) contributes to the regulation of replication-dependent canonical histone gene expression

BACKGROUND: Core canonical histones are required in the S phase of the cell cycle to pack newly synthetized DNA, therefore the expression of their genes is highly activated during DNA replication. In mammalian cells, this increment is achieved by both enhanced transcription and 3′ end processing. In...

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Autores principales: Brzek, Aleksandra, Cichocka, Marlena, Dolata, Jakub, Juzwa, Wojciech, Schümperli, Daniel, Raczynska, Katarzyna Dorota
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062981/
https://www.ncbi.nlm.nih.gov/pubmed/30053800
http://dx.doi.org/10.1186/s12867-018-0110-y
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author Brzek, Aleksandra
Cichocka, Marlena
Dolata, Jakub
Juzwa, Wojciech
Schümperli, Daniel
Raczynska, Katarzyna Dorota
author_facet Brzek, Aleksandra
Cichocka, Marlena
Dolata, Jakub
Juzwa, Wojciech
Schümperli, Daniel
Raczynska, Katarzyna Dorota
author_sort Brzek, Aleksandra
collection PubMed
description BACKGROUND: Core canonical histones are required in the S phase of the cell cycle to pack newly synthetized DNA, therefore the expression of their genes is highly activated during DNA replication. In mammalian cells, this increment is achieved by both enhanced transcription and 3′ end processing. In this paper, we described positive cofactor 4 (PC4) as a protein that contributes to the regulation of replication-dependent histone gene expression. RESULTS: We showed that PC4 influences RNA polymerase II recruitment to histone gene loci in a cell cycle-dependent manner. The most important effect was observed in S phase where PC4 knockdown leads to the elevated level of RNA polymerase II on histone genes, which corresponds to the increased total level of those gene transcripts. The opposite effect was caused by PC4 overexpression. Moreover, we found that PC4 has a negative effect on the unique 3′ end processing of histone pre-mRNAs that can be based on the interaction of PC4 with U7 snRNP and CstF64. Interestingly, this effect does not depend on the cell cycle. CONCLUSIONS: We conclude that PC4 might repress RNA polymerase II recruitment and transcription of replication-dependent histone genes in order to maintain the very delicate balance between histone gene expression and DNA synthesis. It guards the cell from excess of histones in S phase. Moreover, PC4 might promote the interaction of cleavage and polyadenylation complex with histone pre-mRNAs, that might impede with the recruitment of histone cleavage complex. This in turn decreases the 3′ end processing efficiency of histone gene transcripts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12867-018-0110-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-60629812018-07-31 Positive cofactor 4 (PC4) contributes to the regulation of replication-dependent canonical histone gene expression Brzek, Aleksandra Cichocka, Marlena Dolata, Jakub Juzwa, Wojciech Schümperli, Daniel Raczynska, Katarzyna Dorota BMC Mol Biol Research Article BACKGROUND: Core canonical histones are required in the S phase of the cell cycle to pack newly synthetized DNA, therefore the expression of their genes is highly activated during DNA replication. In mammalian cells, this increment is achieved by both enhanced transcription and 3′ end processing. In this paper, we described positive cofactor 4 (PC4) as a protein that contributes to the regulation of replication-dependent histone gene expression. RESULTS: We showed that PC4 influences RNA polymerase II recruitment to histone gene loci in a cell cycle-dependent manner. The most important effect was observed in S phase where PC4 knockdown leads to the elevated level of RNA polymerase II on histone genes, which corresponds to the increased total level of those gene transcripts. The opposite effect was caused by PC4 overexpression. Moreover, we found that PC4 has a negative effect on the unique 3′ end processing of histone pre-mRNAs that can be based on the interaction of PC4 with U7 snRNP and CstF64. Interestingly, this effect does not depend on the cell cycle. CONCLUSIONS: We conclude that PC4 might repress RNA polymerase II recruitment and transcription of replication-dependent histone genes in order to maintain the very delicate balance between histone gene expression and DNA synthesis. It guards the cell from excess of histones in S phase. Moreover, PC4 might promote the interaction of cleavage and polyadenylation complex with histone pre-mRNAs, that might impede with the recruitment of histone cleavage complex. This in turn decreases the 3′ end processing efficiency of histone gene transcripts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12867-018-0110-y) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-27 /pmc/articles/PMC6062981/ /pubmed/30053800 http://dx.doi.org/10.1186/s12867-018-0110-y Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Brzek, Aleksandra
Cichocka, Marlena
Dolata, Jakub
Juzwa, Wojciech
Schümperli, Daniel
Raczynska, Katarzyna Dorota
Positive cofactor 4 (PC4) contributes to the regulation of replication-dependent canonical histone gene expression
title Positive cofactor 4 (PC4) contributes to the regulation of replication-dependent canonical histone gene expression
title_full Positive cofactor 4 (PC4) contributes to the regulation of replication-dependent canonical histone gene expression
title_fullStr Positive cofactor 4 (PC4) contributes to the regulation of replication-dependent canonical histone gene expression
title_full_unstemmed Positive cofactor 4 (PC4) contributes to the regulation of replication-dependent canonical histone gene expression
title_short Positive cofactor 4 (PC4) contributes to the regulation of replication-dependent canonical histone gene expression
title_sort positive cofactor 4 (pc4) contributes to the regulation of replication-dependent canonical histone gene expression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062981/
https://www.ncbi.nlm.nih.gov/pubmed/30053800
http://dx.doi.org/10.1186/s12867-018-0110-y
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