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Histone hypoacetylation is required to maintain late replication timing of constitutive heterochromatin

Casas-Delucchi, Corella S. ; Bemmel, Joke G. van ; Haase, Sebastian ; Herce, Henry D. ; Nowak, Danny ; Meilinger, Daniela ; Stear, Jeffrey H. ; Leonhardt, Heinrich ; Cardoso, M. Cristina (2012)
Histone hypoacetylation is required to maintain late replication timing of constitutive heterochromatin.
In: Nucleic acids research, 40 (1)
Article, Bibliographie

Abstract

The replication of the genome is a spatio-temporally highly organized process. Yet, its flexibility throughout development suggests that this process is not genetically regulated. However, the mechanisms and chromatin modifications controlling replication timing are still unclear. We made use of the prominent structure and defined heterochromatic landscape of pericentric regions as an example of late replicating constitutive heterochromatin. We manipulated the major chromatin markers of these regions, namely histone acetylation, DNA and histone methylation, as well as chromatin condensation and determined the effects of these altered chromatin states on replication timing. Here, we show that manipulation of DNA and histone methylation as well as acetylation levels caused large-scale heterochromatin decondensation. Histone demethylation and the concomitant decondensation, however, did not affect replication timing. In contrast, immuno-FISH and time-lapse analyses showed that lowering DNA methylation, as well as increasing histone acetylation, advanced the onset of heterochromatin replication. While dnmt1(-)(/)(-) cells showed increased histone acetylation at chromocenters, histone hyperacetylation did not induce DNA demethylation. Hence, we propose that histone hypoacetylation is required to maintain normal heterochromatin duplication dynamics. We speculate that a high histone acetylation level might increase the firing efficiency of origins and, concomitantly, advances the replication timing of distinct genomic regions.

Item Type: Article
Erschienen: 2012
Creators: Casas-Delucchi, Corella S. ; Bemmel, Joke G. van ; Haase, Sebastian ; Herce, Henry D. ; Nowak, Danny ; Meilinger, Daniela ; Stear, Jeffrey H. ; Leonhardt, Heinrich ; Cardoso, M. Cristina
Type of entry: Bibliographie
Title: Histone hypoacetylation is required to maintain late replication timing of constitutive heterochromatin
Language: English
Date: 2012
Journal or Publication Title: Nucleic acids research
Volume of the journal: 40
Issue Number: 1
URL / URN: http://www.cardoso-lab.org/publications/Casas-Delucchi 2011b...
Abstract:

The replication of the genome is a spatio-temporally highly organized process. Yet, its flexibility throughout development suggests that this process is not genetically regulated. However, the mechanisms and chromatin modifications controlling replication timing are still unclear. We made use of the prominent structure and defined heterochromatic landscape of pericentric regions as an example of late replicating constitutive heterochromatin. We manipulated the major chromatin markers of these regions, namely histone acetylation, DNA and histone methylation, as well as chromatin condensation and determined the effects of these altered chromatin states on replication timing. Here, we show that manipulation of DNA and histone methylation as well as acetylation levels caused large-scale heterochromatin decondensation. Histone demethylation and the concomitant decondensation, however, did not affect replication timing. In contrast, immuno-FISH and time-lapse analyses showed that lowering DNA methylation, as well as increasing histone acetylation, advanced the onset of heterochromatin replication. While dnmt1(-)(/)(-) cells showed increased histone acetylation at chromocenters, histone hyperacetylation did not induce DNA demethylation. Hence, we propose that histone hypoacetylation is required to maintain normal heterochromatin duplication dynamics. We speculate that a high histone acetylation level might increase the firing efficiency of origins and, concomitantly, advances the replication timing of distinct genomic regions.

Divisions: 10 Department of Biology
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10 Department of Biology > Cell Biology and Epigenetics
Date Deposited: 20 Sep 2011 06:23
Last Modified: 22 Jul 2021 13:02
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