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

Casas-Delucchi, Corella S. and van Bemmel, Joke G. and Haase, Sebastian and Herce, Henry D. and Nowak, Danny and Meilinger, Daniela and Stear, Jeffrey H. and Leonhardt, Heinrich and Cardoso, M. Cristina (2012):
Histone hypoacetylation is required to maintain late replication timing of constitutive heterochromatin.
In: Nucleic acids research, pp. 159-169, 40, (1), ISSN 1362-4962,
[Online-Edition: http://www.cardoso-lab.org/publications/Casas-Delucchi 2011b...],
[Article]

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. and van Bemmel, Joke G. and Haase, Sebastian and Herce, Henry D. and Nowak, Danny and Meilinger, Daniela and Stear, Jeffrey H. and Leonhardt, Heinrich and Cardoso, M. Cristina
Title: Histone hypoacetylation is required to maintain late replication timing of constitutive heterochromatin.
Language: English
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.

Journal or Publication Title: Nucleic acids research
Volume: 40
Number: 1
Divisions: 10 Department of Biology > Cell Biology and Epigenetics
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10 Department of Biology
Date Deposited: 20 Sep 2011 06:23
Official URL: http://www.cardoso-lab.org/publications/Casas-Delucchi 2011b...
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