Epigenetic landscape for initiation of DNA replication

Sherstyuk, Vladimir V.; Shevchenko, Alexander I.; Zakian, Suren M.

doi:10.1007/s00412-013-0448-3

Cited by 20 publications

(24 citation statements)

References 180 publications

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“…In general, euchromatic regions are more enriched with origins that fire early in S-phase, and heterochromatic regions are enriched with origins that fire late. Despite extensive studies of origin firing and its molecular basis (Bell and Dutta 2002;Sherstyuk et al 2013), a number of important questions remain unanswered. A global description of origin firing along chromosomes as cells proceed through S-phase is lacking for any eukaryote; the extent to which origins are randomly distributed or are clustered is not known; it is not clear how many origins are organized into a strictly deterministic program of origin firing; it remains uncertain how the pattern of origin firing contributes to the completion of DNA replication; and the relationship of origins with nuclear replication foci is unclear.…”

Section: Wc2a 3ly United Kingdommentioning

confidence: 99%

The spatial and temporal organization of origin firing during the S-phase of fission yeast

Kaykov

Nurse

2015

Genome Res.

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Eukaryotes duplicate their genomes using multiple replication origins, but the organization of origin firing along chromosomes and during S-phase is not well understood. Using fission yeast, we report the first genome-wide analysis of the spatial and temporal organization of replication origin firing, analyzed using single DNA molecules that can approach the full length of chromosomes. At S-phase onset, origins fire randomly and sparsely throughout the chromosomes. Later in S-phase, clusters of fired origins appear embedded in the sparser regions, which form the basis of nuclear replication foci. The formation of clusters requires proper histone methylation and acetylation, and their locations are not inherited between cell cycles. The rate of origin firing increases gradually, peaking just before mid S-phase. Toward the end of S-phase, nearly all the available origins within the unreplicated regions are fired, contributing to the timely completion of genome replication. We propose that the majority of origins do not fire as a part of a deterministic program. Instead, origin firing, both individually and as clusters, should be viewed as being mostly stochastic.

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Section: Wc2a 3ly United Kingdommentioning

confidence: 99%

The spatial and temporal organization of origin firing during the S-phase of fission yeast

Kaykov

Nurse

2015

Genome Res.

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“…[13][14][15][16] However, it is poorly understood how replication and transcription timing are co-regulated in origins localized at a promoter region. In the present study, we examined the relationship between replication and transcription during cell cycle at the Dbf4 model using high-resolution ChIP in a synchronized cell population.…”

Section: Discussionmentioning

confidence: 99%

“…[13][14][15][16] These modifications may be directly relevant to the opening of chromatin structure and thus transcription activities. This notion is consistent with the observation that the transcriptionally active euchromatin region is replicated during early S phase while heterochromatin is replicated later.…”

Section: Introductionmentioning

confidence: 99%

Dynamic regulation of histone H3K9 is linked to the switch between replication and transcription at the Dbf4 origin-promoter locus

et al. 2016

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The co-regulation of DNA replication and gene transcription is still poorly understood. To gain a better understanding of this important control mechanism, we examined the DNA replication and transcription using the Dbf4 origin-promoter and Dbf4 pseudogene models. We found that origin firing and Dbf4 transcription activity were inversely regulated in a cell cycle-dependent manner. We also found that proteins critical for the regulation of replication (ORC, MCM), transcription (SP1, TFIIB), and cohesin (Smc1, Smc3) and Mediator functions (Med1, Med12) interact with specific sites within and the surrounding regions of the Dbf4 locus in a cell cycle-dependent manner. As expected, replication initiation occurred within a nucleosome-depleted region, and nucleosomes flanked the 2 replication initiation zones. Further, the histone H3 in this region was distinctly acetylated or trimethylated on lysine 9 in a cell cycledependent fluctuation pattern: H3K9ac was most prevalent when the Dbf4 transcription level was highest whereas the H3K9me3 level was greatest during and just after replication. The KDM4A histone demethylase, which is responsible for the H3K9me3 modification, was enriched at the Dbf4 origin in a manner coinciding with H3K9me3. Finally, HP1g, a protein known to interact with H3K9me3 in the heterochromatin was also found enriched at the origin during DNA replication, indicating that H3K9me3 may be required for the regulation of replication at both heterochromatin and euchromatin regions. Taken together, our data show that mammalian cells employ an extremely sophisticated and multilayered co-regulation mechanism for replication and transcription in a highly coordinated manner.

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“…For example, placement of origins near transcription start sites might affect transcription levels and prevent transcription-replication collisions or might reflect a consequence of the enhanced chromatin accessibility near transcriptionally active regions. Similarly, G-quadruplex forming sequences often associate with promoters, euchromatin, and CpG islands [31] and their locations near replication origins might either imply an effect on replication or reflect negative selection against both G-quadruplexes and origins in gene bodies [32]. G-quadruplexes’ ability to interfere with replication fork progression [32] and the requirement for specialized helicases for their unwinding [33,34] might provide an additional selective factor favoring origin-proximal G-quadruplexes.…”

Section: Distribution and Sequence Determinants Of Replication Originsmentioning

confidence: 99%

“…Similarly, G-quadruplex forming sequences often associate with promoters, euchromatin, and CpG islands [31] and their locations near replication origins might either imply an effect on replication or reflect negative selection against both G-quadruplexes and origins in gene bodies [32]. G-quadruplexes’ ability to interfere with replication fork progression [32] and the requirement for specialized helicases for their unwinding [33,34] might provide an additional selective factor favoring origin-proximal G-quadruplexes. An analysis of allele-specific origins suggests that the genetic determinants of origin activity are base composition asymmetry and high GC content rather than the ability to form quadruplexes [25,35].…”

Section: Distribution and Sequence Determinants Of Replication Originsmentioning

confidence: 99%

Replication origins: determinants or consequences of nuclear organization?

Marks¹,

Smith²,

Aladjem³

2016

Current Opinion in Genetics & Development

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Chromosome replication, gene expression and chromatin assembly all occur on the same template, necessitating a tight spatial and temporal coordination to maintain genomic stability. The distribution of replication initiation events is responsive to local and global changes in chromatin structure and is affected by transcriptional activity. Concomitantly, replication origin sequences, which determine the locations of replication initiation events, can affect chromatin structure and modulate transcriptional efficiency. The flexibility observed in the replication initiation landscape might help achieve complete and accurate genome duplication while coordinating the DNA replication program with transcription and other nuclear processes in a cell-type specific manner. This review discusses the relationships among replication origin distribution, local and global chromatin structures and concomitant nuclear metabolic processes.

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Epigenetic landscape for initiation of DNA replication

Cited by 20 publications

References 180 publications

The spatial and temporal organization of origin firing during the S-phase of fission yeast

The spatial and temporal organization of origin firing during the S-phase of fission yeast

Dynamic regulation of histone H3K9 is linked to the switch between replication and transcription at the Dbf4 origin-promoter locus

Replication origins: determinants or consequences of nuclear organization?

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