Genome-wide approaches to determining origin distribution

Cadoret, Jean‐Charles; Prioleau, Marie‐Noëlle

doi:10.1007/s10577-009-9094-2

Cited by 14 publications

(13 citation statements)

References 35 publications

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“…In silico analysis of these origins revealed that ∼43% of origins possess E-box element (Supplementary Table S4). However, the regulation of origins by c-Myc occupancy could be under the tight temporal control as evident from ChIP-on-chip data reported recently (44). To further elucidate the molecular underpinnings of temporally programmed c-Myc occupancy, we used methylation-sensitive restriction analysis (MSRA) for the E-box element as it is well known that methylated E-box (mE-box) could not recruit c-Myc.…”

Section: Resultsmentioning

confidence: 84%

The epigenetic control of E-box and Myc-dependent chromatin modifications regulate the licensing of lamin B2 origin during cell cycle

Swarnalatha

Singh

Kumar

2012

Nucleic Acids Research

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Recent genome-wide mapping of the mammalian replication origins has suggested the role of transcriptional regulatory elements in origin activation. However, the nature of chromatin modifications associated with such trans-factors or epigenetic marks imprinted on cis-elements during the spatio-temporal regulation of replication initiation remains enigmatic. To unveil the molecular underpinnings, we studied the human lamin B2 origin that spatially overlaps with TIMM 13 promoter. We observed an early G1-specific occupancy of c-Myc that facilitated the loading of mini chromosome maintenance protein (MCM) complex during subsequent mid-G1 phase rather stimulating TIMM 13 gene expression. Investigations on the Myc-induced downstream events suggested a direct interaction between c-Myc and histone methyltransferase mixed-lineage leukemia 1 that imparted histone H3K4me3 mark essential for both recruitment of acetylase complex HBO1 and hyperacetylation of histone H4. Contemporaneously, the nucleosome remodeling promoted the loading of MCM proteins at the origin. These chromatin modifications were under the tight control of active demethylation of E-box as evident from methylation profiling. The active demethylation was mediated by the Ten-eleven translocation (TET)-thymine DNA glycosylase-base excision repair (BER) pathway, which facilitated spatio-temporal occupancy of Myc. Intriguingly, the genome-wide 43% occurrence of E-box among the human origins could support our hypothesis that epigenetic control of E-box could be a molecular switch for the licensing of early replicating origins.

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Section: Resultsmentioning

confidence: 84%

The epigenetic control of E-box and Myc-dependent chromatin modifications regulate the licensing of lamin B2 origin during cell cycle

Swarnalatha

Singh

Kumar

2012

Nucleic Acids Research

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“…Although the CHO DHFR locus is one of the most well-studied initiation zones, different results have provided different interpretations of the frequency with which replication initiates at different sites within the zone, often referred to as ‘origin efficiency’ (30,42). The most direct means to evaluate origin efficiency is by examining the location and frequency of initiation sites on individual DNA fibers, and this method has not been applied to study initiation at the CHO DHFR locus.…”

Section: Resultsmentioning

confidence: 99%

Pre-replication complex proteins assemble at regions of low nucleosome occupancy within the Chinese hamster dihydrofolate reductase initiation zone

Lubelsky

Sasaki

Kuipers

et al. 2010

Nucleic Acids Research

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Genome-scale mapping of pre-replication complex proteins has not been reported in mammalian cells. Poor enrichment of these proteins at specific sites may be due to dispersed binding, poor epitope availability or cell cycle stage-specific binding. Here, we have mapped sites of biotin-tagged ORC and MCM protein binding in G1-synchronized populations of Chinese hamster cells harboring amplified copies of the dihydrofolate reductase (DHFR) locus, using avidin-affinity purification of biotinylated chromatin followed by high-density microarray analysis across the DHFR locus. We have identified several sites of significant enrichment for both complexes distributed throughout the previously identified initiation zone. Analysis of the frequency of initiations across stretched DNA fibers from the DHFR locus confirmed a broad zone of de-localized initiation activity surrounding the sites of ORC and MCM enrichment. Mapping positions of mononucleosomal DNA empirically and computing nucleosome-positioning information in silico revealed that ORC and MCM map to regions of low measured and predicted nucleosome occupancy. Our results demonstrate that specific sites of ORC and MCM enrichment can be detected within a mammalian intitiation zone, and suggest that initiation zones may be regions of generally low nucleosome occupancy where flexible nucleosome positioning permits flexible pre-RC assembly sites.

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“…These short (80-120 bp) origins of replication contain an essential, conserved element called the ARS consensus sequence (ACS) that is bound by the eukaryotic initiator, the origin recognition complex (ORC, Bell and Dutta, 2002). With the exception of some embryonic tissues, the initiation of replication in metazoan organisms also occurs at reproducible positions, however, no consensus sequence is associated with these sites (Cadoret and Prioleau, 2010). Although in vitro assays for the initial helicase loading event at a defined origin exist (Remus and Diffley, 2009), the loaded helicases are inactive and assays for their activation and for origin-dependent replication initiation have not been described.…”

Section: Introductionmentioning

confidence: 99%

Eukaryotic Origin-Dependent DNA Replication In Vitro Reveals Sequential Action of DDK and S-CDK Kinases

Heller

Kang

Lam

et al. 2011

Cell

285

370

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Summary Proper eukaryotic DNA replication requires temporal separation of helicase loading from helicase activation and replisome assembly. Using an in vitro assay for eukaryotic origin-dependent replication initiation, we investigated the control of these events. After helicase loading, we found that the Dbf4-dependent Cdc7 kinase (DDK) initially drives origin recruitment of Sld3 and the Cdc45 helicase-activating protein. Corresponding, in vivo studies demonstrate that DDK drives early-firing origin recruitment of Cdc45 before S-CDK activation. Upon activation of S-phase cyclin-dependent kinases (S-CDK), a second helicase-activating protein (GINS) and the remainder of the replisome are recruited to the origin. Investigation of DNA polymerase recruitment showed that Mcm10 and DNA unwinding both were critical for recruitment of lagging but not leading strand DNA polymerases. Our studies identify distinct roles for DDK and S-CDK during helicase activation and support a model in which leading strand DNA polymerases are recruited prior to origin DNA unwinding and RNA primer synthesis.

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Genome-wide approaches to determining origin distribution

Cited by 14 publications

References 35 publications

The epigenetic control of E-box and Myc-dependent chromatin modifications regulate the licensing of lamin B2 origin during cell cycle

The epigenetic control of E-box and Myc-dependent chromatin modifications regulate the licensing of lamin B2 origin during cell cycle

Pre-replication complex proteins assemble at regions of low nucleosome occupancy within the Chinese hamster dihydrofolate reductase initiation zone

Eukaryotic Origin-Dependent DNA Replication In Vitro Reveals Sequential Action of DDK and S-CDK Kinases

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