Chromatin unfolding by Cdt1 regulates MCM loading via opposing functions of HBO1 and HDAC11-geminin

Wong, Philip G.; Glozak, Michele A.; Cao, Thinh V.; Vaziri, Cyrus; Seto, Edward; Alexandrow, Mark G.

doi:10.4161/cc.9.21.13596

Cited by 57 publications

(69 citation statements)

References 52 publications

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“…Hbo1 association to origins is dependent on Cdt1, and it has been shown that Cdt1 can modulate chromatin accessibility through temporal recruitment of Hbo1 to origins (Miotto and Struhl, 2008). Interestingly, ectopic tethering of Cdt1 is also known to induce large-scale chromatin unfolding at a transgene array (Wong et al, 2010). It is well established that the origins comprise open chromatin during G1 and then become less accessible as cells exit out of G1 phase (Djeliova et al, 2002;Pemov et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…The replication origins are known to exhibit temporal dynamics in chromatin structure, with a highly open structure during G1 and more closed architecture during S phase. Elegant work, using a quantitative-PCR-based approach on DNase-1-treated chromatin samples, has shown that endogenous replication origins, including those of MCM4 and lamin, display a more open chromatin structure during G1 than in S phase (Wong et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

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Orc5 induces large-scale chromatin decondensation in a GCN5-dependent manner

Giri

Chakraborty

Sathyan

et al. 2015

Journal of Cell Science

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In eukaryotes, origin recognition complex (ORC) proteins establish the pre-replicative complex ( preRC) at the origins, and this is essential for the initiation of DNA replication. Open chromatin structures regulate the efficiency of preRC formation and replication initiation. However, the molecular mechanisms that control chromatin structure, and how the preRC components establish themselves on the chromatin remain to be understood. In human cells, the ORC is a highly dynamic complex with many separate functions attributed to sub-complexes or individual subunits of the ORC, including heterochromatin organization, telomere and centromere function, centrosome duplication and cytokinesis. We demonstrate that human Orc5, unlike other ORC subunits, when ectopically tethered to a chromatin locus, induces large-scale chromatin decondensation, predominantly during G1 phase of the cell cycle. Orc5 associates with the H3 histone acetyl transferase GCN5 (also known as KAT2A), and this association enhances the chromatin-opening function of Orc5. In the absence of Orc5, histone H3 acetylation is decreased at the origins. We propose that the ability of Orc5 to induce chromatin unfolding during G1 allows the establishment of the preRC at the origins.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Orc5 induces large-scale chromatin decondensation in a GCN5-dependent manner

Giri

Chakraborty

Sathyan

et al. 2015

Journal of Cell Science

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“…99,119 Supporting the positive role of histone acetylation levels on replication in human cells, Cdt1-mediated recruitment of the human HBO1, before the onset of S-phase, plays a role in replication by increasing H4 acetylation, chromatin decondensation and subsequently enhancing MCM recruitment. 120 Indeed, HBO1 knockdown results in a decrease in DNA synthesis and affects progression through S-phase. Importantly, it is the acetylating activity of HBO1 that was necessary for MCM recruitment.…”

Section: Epigenetics and Dna Replication Timing In Mammalsmentioning

confidence: 99%

“…30,121 This effect is counteracted by HDAC11, another partner of Cdt1, which is active during S-phase, prevents MCM recruitment and thereby avoids re-replication. 120 Nevertheless, transcription and the associated open chromatin have been proposed to correlate better with early replication timing rather than replication activity itself. In fact, early origins correlate with actively transcribed genes, while late origins are located in non-transcribed regions.…”

Section: Epigenetics and Dna Replication Timing In Mammalsmentioning

confidence: 99%

Epigenetic control of DNA replication dynamics in mammals

Casas-Delucchi

Cardoso

2011

Nucleus

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“…Several studies have demonstrated that the acetylation of nucleosomes promotes ORC binding, active origin selection and early replication initiation during S phase (Aggarwal and Calvi, 2004;Danis et al, 2004;Hartl et al, 2007;Kim et al, 2011;Pappas et al, 2004;Schwaiger et al, 2009;Vogelauer et al, 2002). Moreover, a number of specific histone acetyltransferases (HATs) and histone deacetylases (HDACs) have been shown to influence origin activity (Aggarwal and Calvi, 2004;Doyon et al, 2006;Espinosa et al, 2010;Iizuka et al, 2006;Iizuka and Stillman, 1999;Karmakar et al, 2010;Miotto and Struhl, 2008;Miotto and Struhl, 2010;Pappas et al, 2004;Vogelauer et al, 2002;Wong et al, 2010). Nevertheless, how different HATs and HDACS regulate origins in concert with development remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

The histone acetyltransferases CBP and Chameau integrate developmental and DNA replication programs in Drosophila ovarian follicle cells

2012

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SUMMARYDNA replication origin activity changes during development. Chromatin modifications are known to influence the genomic location of origins and the time during S phase that they initiate replication in different cells. However, how chromatin regulates origins in concert with cell differentiation remains poorly understood. Here, we use developmental gene amplification in Drosophila ovarian follicle cells as a model to investigate how chromatin modifiers regulate origins in a developmental context. We find that the histone acetyltransferase (HAT) Chameau (Chm) binds to amplicon origins and is partially required for their function. Depletion of Chm had relatively mild effects on origins during gene amplification and genomic replication compared with previous knockdown of its ortholog HBO1 in human cells, which has severe effects on origin function. We show that another HAT, CBP (Nejire), also binds amplicon origins and is partially required for amplification. Knockdown of Chm and CBP together had a more severe effect on nucleosome acetylation and amplicon origin activity than knockdown of either HAT alone, suggesting that these HATs collaborate in origin regulation. In addition to their local function at the origin, we show that Chm and CBP also globally regulate the developmental transition of follicle cells into the amplification stages of oogenesis. Our results reveal a complexity of origin epigenetic regulation by multiple HATs during development and suggest that chromatin modifiers are a nexus that integrates differentiation and DNA replication programs.

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Chromatin unfolding by Cdt1 regulates MCM loading via opposing functions of HBO1 and HDAC11-geminin

Cited by 57 publications

References 52 publications

Orc5 induces large-scale chromatin decondensation in a GCN5-dependent manner

Orc5 induces large-scale chromatin decondensation in a GCN5-dependent manner

Epigenetic control of DNA replication dynamics in mammals

The histone acetyltransferases CBP and Chameau integrate developmental and DNA replication programs in Drosophila ovarian follicle cells

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