Conservation of Epigenetic Regulation, ORC Binding and Developmental Timing of DNA Replication Origins in the Genus Drosophila

Calvi, Brian R.; Byrnes, B. A.; Kolpakas, Alexis

doi:10.1534/genetics.107.070862

Cited by 23 publications

(20 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, in higher eukaryotes, early replication correlates with a high probability of transcription and the presence of histone modifications characteristic of active chromatin such as histone acetylation (Schwaiger et al 2009;Hansen et al 2010). Histone hyperacetylation has been directly implicated to facilitate origin activation and thereby early replication timing (Aggarwal and Calvi 2004;Calvi et al 2007;Goren et al 2008) in agreement with a model of a function for open chromatin. If origin definition and activation would be purely defined by chromatin, one might expect that any relief of gene repression will lead to early replication at any chromosomal position.…”

mentioning

confidence: 71%

Heterochromatin protein 1 (HP1) modulates replication timing of the Drosophila genome

Schwaiger¹,

Kohler²,

Oakeley³

et al. 2010

Genome Res.

View full text Add to dashboard Cite

The replication of a chromosomal region during S phase can be highly dynamic between cell types that differ in transcriptome and epigenome. Early replication timing has been positively correlated with several histone modifications that occur at active genes, while repressive histone modifications mark late replicating regions. This raises the question if chromatin modulates the initiating events of replication. To gain insights into this question, we have studied the function of heterochromatin protein 1 (HP1), which is a reader of repressive methylation at histone H3 lysine 9, in genome-wide organization of replication. Cells with reduced levels of HP1 show an advanced replication timing of centromeric repeats in agreement with the model that repressive chromatin mediates the very late replication of large clusters of constitutive heterochromatin. Surprisingly, however, regions with high levels of interspersed repeats on the chromosomal arms, in particular on chromosome 4 and in pericentromeric regions of chromosome 2, behave differently. Here, loss of HP1 results in delayed replication. The fact that these regions are bound by HP1 suggests a direct effect. Thus while HP1 mediates very late replication of centromeric DNA, it is also required for early replication of euchromatic regions with high levels of repeats. This observation of opposing functions of HP1 suggests a model where HP1-mediated repeat inactivation or replication complex loading on the chromosome arms is required for proper activation of origins of replication that fire early. At the same time, HP1-mediated repression at constitutive heterochromatin is required to ensure replication of centromeric repeats at the end of S phase.

show abstract

mentioning

confidence: 71%

Heterochromatin protein 1 (HP1) modulates replication timing of the Drosophila genome

Schwaiger¹,

Kohler²,

Oakeley³

et al. 2010

Genome Res.

View full text Add to dashboard Cite

show abstract

“…5). Several single-gene studies have suggested a positive function of histone acteylation for origin activity (Lin et al 2003;Aggarwal and Calvi 2004;Danis et al 2004;Calvi et al 2007;Hartl et al 2007;Goren et al 2008). Other reports, however, did not support this model (Prioleau et al 2003;Dazy et al 2006;Gregoire et al 2006).…”

Section: H4k16 Acetylation Links Chromatin With Early Replication Andmentioning

confidence: 97%

Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome

Schwaiger¹,

Stadler²,

Bell³

et al. 2009

Genes Dev.

146

265

View full text Add to dashboard Cite

Duplication of eukaryotic genomes during S phase is coordinated in space and time. In order to identify zones of initiation and cell-type-as well as gender-specific plasticity of DNA replication, we profiled replication timing, histone acetylation, and transcription throughout the Drosophila genome. We observed two waves of replication initiation with many distinct zones firing in early-S phase and multiple, less defined peaks at the end of S phase, suggesting that initiation becomes more promiscuous in late-S phase. A comparison of different cell types revealed widespread plasticity of replication timing on autosomes. Most occur in large regions, but only half coincide with local differences in transcription. In contrast to confined autosomal differences, a global shift in replication timing occurs throughout the single male X chromosome. Unlike in females, the dosage-compensated X chromosome replicates almost exclusively early. This difference occurs at sites that are not transcriptionally hyperactivated, but show increased acetylation of Lys 16 of histone H4 (H4K16ac). This suggests a transcription-independent, yet chromosome-wide process related to chromatin. Importantly, H4K16ac is also enriched at initiation zones as well as early replicating regions on autosomes during S phase. Together, our study reveals novel organizational principles of DNA replication of the Drosophila genome and suggests that H4K16ac is more closely correlated with replication timing than is transcription.[Keywords: Chromatin; Drosophila; microarray; replication] Supplemental material is available at http://www.genesdev.org.

show abstract

“…Transcription factors at sites of replication initiation have been shown to stimulate replication in many systems, including viruses, yeast, Drosophila, and Xenopus (8,9). This stimulation may be a consequence of direct interaction with components of the replication machinery or of facilitating the access of the replication complexes to DNA through recruitment of chromatin remodeling complexes (10)(11)(12). Here we present a high-resolution map of replication origins in HeLa cells based on hybridization of short nascent strands (SNS) on DNA microarrays covering ENCODE regions.…”

mentioning

confidence: 99%

Genome-wide studies highlight indirect links between human replication origins and gene regulation

Cadoret

Meisch

Hassan‐Zadeh

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

275

334

View full text Add to dashboard Cite

To get insights into the regulation of replication initiation, we systematically mapped replication origins along 1% of the human genome in HeLa cells. We identified 283 origins, 10 times more than previously known. Origin density is strongly correlated with genomic landscapes, with clusters of closely spaced origins in GC-rich regions and no origins in large GC-poor regions. Origin sequences are evolutionarily conserved, and half of them map within or near CpG islands. Most of the origins overlap transcriptional regulatory elements, providing further evidence of a connection with gene regulation. Moreover, we identify c-JUN and c-FOS as important regulators of origin selection. Half of the identified replication initiation sites do not have an open chromatin configuration, showing the absence of a direct link with gene regulation. Replication timing analyses coupled with our origin mapping suggest that a relatively strict origintiming program regulates the replication of the human genome.chromatin structure ͉ DNA replication origin ͉ ENCODE regions ͉ genome-wide mapping ͉ CpG island C ontrolling the number of origins from which replication begins in a given chromosome is necessary to protect it from instability (1, 2). Mapping DNA replication starting points, known as ''origins of replication,'' would make a large contribution to understanding how genome replication is coordinated. Identification of a large number of replication origins is necessary to decipher the rules of origin specification. However, fewer than 30 origins have been identified in human cells (3), and they were mapped mostly in well-characterized transcribed regions, leaving gene-poor regions unexplored. The Encyclopedia of DNA Elements (ENCODE) project (4), launched to develop high-throughput methods for identifying functional elements, now provides a comprehensive view of gene expression and chromatin structure along 1% of the human genome (30 Mb, 44 regions) (5); it thus provides a powerful model for studying interactions among chromosome organization, gene regulation, and initiation of DNA replication. Origin selection is initiated by the binding of the origin recognition complex (ORC) to origin-proximal DNA sequences (6). In contrast to Saccharomyces cerevisiae, characterized metazoan origins do not conform to a clear consensus sequence, and the ORCs from higher eukaryotes exhibit no sequence specificity in vitro (7). Transcription factors at sites of replication initiation have been shown to stimulate replication in many systems, including viruses, yeast, Drosophila, and Xenopus (8, 9). This stimulation may be a consequence of direct interaction with components of the replication machinery or of facilitating the access of the replication complexes to DNA through recruitment of chromatin remodeling complexes (10-12). Here we present a high-resolution map of replication origins in HeLa cells based on hybridization of short nascent strands (SNS) on DNA microarrays covering ENCODE regions. To construct this map we use one of the most string...

show abstract

Conservation of Epigenetic Regulation, ORC Binding and Developmental Timing of DNA Replication Origins in the Genus Drosophila

Cited by 23 publications

References 64 publications

Heterochromatin protein 1 (HP1) modulates replication timing of the Drosophila genome

Heterochromatin protein 1 (HP1) modulates replication timing of the Drosophila genome

Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome

Genome-wide studies highlight indirect links between human replication origins and gene regulation

Contact Info

Product

Resources

About