DNA replication timing influences gene expression level

Müller, Carolin A. and Nieduszynski, Conrad A. ORCID: https://orcid.org/0000-0003-2001-076X (2017) DNA replication timing influences gene expression level. Journal of Cell Biology, 216 (7). pp. 1907-1914. ISSN 0021-9525

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Eukaryotic genomes are replicated in a reproducible temporal order; however, the physiological significance is poorly understood. We compared replication timing in divergent yeast species and identified genomic features with conserved replication times. Histone genes were among the earliest replicating loci in all species. We specifically delayed the replication of HTA1-HTB1 and discovered that this halved the expression of these histone genes. Finally, we showed that histone and cell cycle genes in general are exempt from Rtt109-dependent dosage compensation, suggesting the existence of pathways excluding specific loci from dosage compensation mechanisms. Thus, we have uncovered one of the first physiological requirements for regulated replication time and demonstrated a direct link between replication timing and gene expression.

Item Type: Article
Additional Information: Funding Information: We are grateful to Gianni Liti, Edward Louis, and Ken Wolfe for kindly providing strains. We thank Nieduszynski group members for helpful discussion and advice; Peter Cook, Nick Proudfoot, and Adam Grieve for critical reading of the manuscript; and Naama Barkai and Yoak Voichek for kindly sharing published expression data and offering advice on its analysis. We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust, grant reference 090532/Z/09/Z) for the generation of the high-throughput sequencing data. This work was supported by Biotechnology and Biological Sciences Research Council grants BB/N016858/1 and BB/K007211/1 and Wellcome Trust Investigator Award 110064/Z/15/Z. Publisher Copyright: © 2017 Müller and Nieduszynski.
Uncontrolled Keywords: cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1307
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 07 Sep 2022 14:31
Last Modified: 21 Oct 2022 01:37
URI: https://ueaeprints.uea.ac.uk/id/eprint/87861
DOI: 10.1083/jcb.201701061

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