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Human ORC/MCM density is low in active genes and correlates with replication time but does not delimit initiation zones
Eukaryotic DNA replication initiates during S phase from origins that have been licensed in the preceding G1 phase. Here, we compare ChIP-seq profiles of the licensing factors Orc2, Orc3, Mcm3, and Mcm7 with gene expression, replication timing, and fork directionality profiles obtained by RNA-seq, R...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993996/ https://www.ncbi.nlm.nih.gov/pubmed/33683199 http://dx.doi.org/10.7554/eLife.62161 |
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author | Kirstein, Nina Buschle, Alexander Wu, Xia Krebs, Stefan Blum, Helmut Kremmer, Elisabeth Vorberg, Ina M Hammerschmidt, Wolfgang Lacroix, Laurent Hyrien, Olivier Audit, Benjamin Schepers, Aloys |
author_facet | Kirstein, Nina Buschle, Alexander Wu, Xia Krebs, Stefan Blum, Helmut Kremmer, Elisabeth Vorberg, Ina M Hammerschmidt, Wolfgang Lacroix, Laurent Hyrien, Olivier Audit, Benjamin Schepers, Aloys |
author_sort | Kirstein, Nina |
collection | PubMed |
description | Eukaryotic DNA replication initiates during S phase from origins that have been licensed in the preceding G1 phase. Here, we compare ChIP-seq profiles of the licensing factors Orc2, Orc3, Mcm3, and Mcm7 with gene expression, replication timing, and fork directionality profiles obtained by RNA-seq, Repli-seq, and OK-seq. Both, the origin recognition complex (ORC) and the minichromosome maintenance complex (MCM) are significantly and homogeneously depleted from transcribed genes, enriched at gene promoters, and more abundant in early- than in late-replicating domains. Surprisingly, after controlling these variables, no difference in ORC/MCM density is detected between initiation zones, termination zones, unidirectionally replicating regions, and randomly replicating regions. Therefore, ORC/MCM density correlates with replication timing but does not solely regulate the probability of replication initiation. Interestingly, H4K20me3, a histone modification proposed to facilitate late origin licensing, was enriched in late-replicating initiation zones and gene deserts of stochastic replication fork direction. We discuss potential mechanisms specifying when and where replication initiates in human cells. |
format | Online Article Text |
id | pubmed-7993996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-79939962021-03-26 Human ORC/MCM density is low in active genes and correlates with replication time but does not delimit initiation zones Kirstein, Nina Buschle, Alexander Wu, Xia Krebs, Stefan Blum, Helmut Kremmer, Elisabeth Vorberg, Ina M Hammerschmidt, Wolfgang Lacroix, Laurent Hyrien, Olivier Audit, Benjamin Schepers, Aloys eLife Chromosomes and Gene Expression Eukaryotic DNA replication initiates during S phase from origins that have been licensed in the preceding G1 phase. Here, we compare ChIP-seq profiles of the licensing factors Orc2, Orc3, Mcm3, and Mcm7 with gene expression, replication timing, and fork directionality profiles obtained by RNA-seq, Repli-seq, and OK-seq. Both, the origin recognition complex (ORC) and the minichromosome maintenance complex (MCM) are significantly and homogeneously depleted from transcribed genes, enriched at gene promoters, and more abundant in early- than in late-replicating domains. Surprisingly, after controlling these variables, no difference in ORC/MCM density is detected between initiation zones, termination zones, unidirectionally replicating regions, and randomly replicating regions. Therefore, ORC/MCM density correlates with replication timing but does not solely regulate the probability of replication initiation. Interestingly, H4K20me3, a histone modification proposed to facilitate late origin licensing, was enriched in late-replicating initiation zones and gene deserts of stochastic replication fork direction. We discuss potential mechanisms specifying when and where replication initiates in human cells. eLife Sciences Publications, Ltd 2021-03-08 /pmc/articles/PMC7993996/ /pubmed/33683199 http://dx.doi.org/10.7554/eLife.62161 Text en © 2021, Kirstein et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Chromosomes and Gene Expression Kirstein, Nina Buschle, Alexander Wu, Xia Krebs, Stefan Blum, Helmut Kremmer, Elisabeth Vorberg, Ina M Hammerschmidt, Wolfgang Lacroix, Laurent Hyrien, Olivier Audit, Benjamin Schepers, Aloys Human ORC/MCM density is low in active genes and correlates with replication time but does not delimit initiation zones |
title | Human ORC/MCM density is low in active genes and correlates with replication time but does not delimit initiation zones |
title_full | Human ORC/MCM density is low in active genes and correlates with replication time but does not delimit initiation zones |
title_fullStr | Human ORC/MCM density is low in active genes and correlates with replication time but does not delimit initiation zones |
title_full_unstemmed | Human ORC/MCM density is low in active genes and correlates with replication time but does not delimit initiation zones |
title_short | Human ORC/MCM density is low in active genes and correlates with replication time but does not delimit initiation zones |
title_sort | human orc/mcm density is low in active genes and correlates with replication time but does not delimit initiation zones |
topic | Chromosomes and Gene Expression |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993996/ https://www.ncbi.nlm.nih.gov/pubmed/33683199 http://dx.doi.org/10.7554/eLife.62161 |
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