Global early replication disrupts gene expression and chromatin conformation in a single cell cycle.

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BACKGROUND: The early embryonic divisions of many organisms, including fish, flies, and frogs, are characterized by a very rapid S-phase caused by high rates of replication initiation. In somatic cells, S-phase is much longer due to both a reduction in the total number of initiation events and the imposition of a temporal order of origin activation. The physiological importance of changes in the rate and timing of replication initiation in S-phase remains unclear. RESULTS: Here we assess the importance of the temporal control of replication initiation using a conditional system in budding yeast to drive the early replication of the majority of origins in a single cell cycle. We show that global early replication disrupts the expression of over a quarter of all genes. By deleting individual origins, we show that delaying replication is sufficient to restore normal gene expression, directly implicating origin firing control in this regulation. Global early replication disrupts nucleosome positioning and transcription factor binding during S-phase, suggesting that the rate of S-phase is important to regulate the chromatin landscape. CONCLUSIONS: Together, these data provide new insight into the role of the temporal control of origin firing during S-phase for coordinating replication, gene expression, and chromatin establishment as occurs in the early embryo.

Cell Cycle, Chromatin, DNA Replication, Gene Expression, Nucleosomes, Replication Origin, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription Factors
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Genome Biol
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BioMed Central
Wellcome Trust (107056/Z/15/Z)
Cancer Research UK (C72647/A30783)
Worldwide Cancer Research (formerly AICR) (10-0908)
BBSRC (1943901)
Biotechnology and Biological Sciences Research Council (BB/M011194/1)
Cancer Research Uk (None)
AICR 10-0908, Wellcome Trust 107056/Z/15/Z, Cancer Research UK C15873/A12700 and Gurdon Institute funding (Cancer Research UK C6946/A14492, Wellcome Trust 092096). The first author was funded by the BBSRC BB/M011194/1 and a Cambridge Trust scholarship.