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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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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. |
format | Online Article Text |
id | pubmed-6062981 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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