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USF Binding Sequences from the HS4 Insulator Element Impose Early Replication Timing on a Vertebrate Replicator
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295818/ https://www.ncbi.nlm.nih.gov/pubmed/22412349 http://dx.doi.org/10.1371/journal.pbio.1001277 |
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author | Hassan-Zadeh, Vahideh Chilaka, Sabarinadh Cadoret, Jean-Charles Ma, Meiji Kit-Wan Boggetto, Nicole West, Adam G. Prioleau, Marie-Noëlle |
author_facet | Hassan-Zadeh, Vahideh Chilaka, Sabarinadh Cadoret, Jean-Charles Ma, Meiji Kit-Wan Boggetto, Nicole West, Adam G. Prioleau, Marie-Noëlle |
author_sort | Hassan-Zadeh, Vahideh |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3295818 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32958182012-03-12 USF Binding Sequences from the HS4 Insulator Element Impose Early Replication Timing on a Vertebrate Replicator Hassan-Zadeh, Vahideh Chilaka, Sabarinadh Cadoret, Jean-Charles Ma, Meiji Kit-Wan Boggetto, Nicole West, Adam G. Prioleau, Marie-Noëlle PLoS Biol Research Article 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. Public Library of Science 2012-03-06 /pmc/articles/PMC3295818/ /pubmed/22412349 http://dx.doi.org/10.1371/journal.pbio.1001277 Text en Hassan-Zadeh et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Hassan-Zadeh, Vahideh Chilaka, Sabarinadh Cadoret, Jean-Charles Ma, Meiji Kit-Wan Boggetto, Nicole West, Adam G. Prioleau, Marie-Noëlle USF Binding Sequences from the HS4 Insulator Element Impose Early Replication Timing on a Vertebrate Replicator |
title | USF Binding Sequences from the HS4 Insulator Element Impose Early Replication Timing on a Vertebrate Replicator |
title_full | USF Binding Sequences from the HS4 Insulator Element Impose Early Replication Timing on a Vertebrate Replicator |
title_fullStr | USF Binding Sequences from the HS4 Insulator Element Impose Early Replication Timing on a Vertebrate Replicator |
title_full_unstemmed | USF Binding Sequences from the HS4 Insulator Element Impose Early Replication Timing on a Vertebrate Replicator |
title_short | USF Binding Sequences from the HS4 Insulator Element Impose Early Replication Timing on a Vertebrate Replicator |
title_sort | usf binding sequences from the hs4 insulator element impose early replication timing on a vertebrate replicator |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295818/ https://www.ncbi.nlm.nih.gov/pubmed/22412349 http://dx.doi.org/10.1371/journal.pbio.1001277 |
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