USF binding sequences from the HS4 insulator element impose early replication timing on a vertebrate replicator

Hassan-Zadeh, V. , Chilaka, S. , Cadoret, J.-C. , Ma, M. , Boggetto, N. , West, A. G. and Prioleau, M.-N. (2012) USF binding sequences from the HS4 insulator element impose early replication timing on a vertebrate replicator. PLoS Biology, 10(3), e1001277. (doi: 10.1371/journal.pbio.1001277) (PMID:22412349) (PMCID:PMC3295818)




The nuclear genomes of vertebrates show a highly organized program of DNA replication where GC-rich isochores are replicated early in S-phase, while AT-rich isochores are late replicating. GC-rich regions are gene dense and are enriched for active transcription, suggesting a connection between gene regulation and replication timing. Insulator elements can organize independent domains of gene transcription and are suitable candidates for being key regulators of replication timing. We have tested the impact of inserting a strong replication origin flanked by the β-globin HS4 insulator on the replication timing of naturally late replicating regions in two different avian cell types, DT40 (lymphoid) and 6C2 (erythroid). We find that the HS4 insulator has the capacity to impose a shift to earlier replication. This shift requires the presence of HS4 on both sides of the replication origin and results in an advance of replication timing of the target locus from the second half of S-phase to the first half when a transcribed gene is positioned nearby. Moreover, we find that the USF transcription factor binding site is the key cis-element inside the HS4 insulator that controls replication timing. Taken together, our data identify a combination of cis-elements that might constitute the basic unit of multi-replicon megabase-sized early domains of DNA replication.

Item Type:Articles
Glasgow Author(s) Enlighten ID:West, Dr Adam and Ma, Miss Meiji
Authors: Hassan-Zadeh, V., Chilaka, S., Cadoret, J.-C., Ma, M., Boggetto, N., West, A. G., and Prioleau, M.-N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:PLoS Biology
Journal Abbr.:PLoS Biol
Publisher:Public Library of Science
ISSN (Online):1545-7885
Published Online:06 March 2012
Copyright Holders:Copyright © 2012 Public Library of Science
First Published:First published in PLoS Biology
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
365431Histone modifications at chromatin boundary elementsAdam WestBiotechnology and Biological Sciences Research Council (BBSRC)BBS/B/08043RI CANCER SCIENCES