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Capture‐C reveals preformed chromatin interactions between HIF‐binding sites and distant promoters

Hypoxia‐inducible factor (HIF) directs an extensive transcriptional cascade that transduces numerous adaptive responses to hypoxia. Pan‐genomic analyses, using chromatin immunoprecipitation and transcript profiling, have revealed large numbers of HIF‐binding sites that are generally associated with...

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Autores principales: Platt, James L, Salama, Rafik, Smythies, James, Choudhry, Hani, Davies, James OJ, Hughes, Jim R, Ratcliffe, Peter J, Mole, David R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048371/
https://www.ncbi.nlm.nih.gov/pubmed/27506891
http://dx.doi.org/10.15252/embr.201642198
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author Platt, James L
Salama, Rafik
Smythies, James
Choudhry, Hani
Davies, James OJ
Hughes, Jim R
Ratcliffe, Peter J
Mole, David R
author_facet Platt, James L
Salama, Rafik
Smythies, James
Choudhry, Hani
Davies, James OJ
Hughes, Jim R
Ratcliffe, Peter J
Mole, David R
author_sort Platt, James L
collection PubMed
description Hypoxia‐inducible factor (HIF) directs an extensive transcriptional cascade that transduces numerous adaptive responses to hypoxia. Pan‐genomic analyses, using chromatin immunoprecipitation and transcript profiling, have revealed large numbers of HIF‐binding sites that are generally associated with hypoxia‐inducible transcripts, even over long chromosomal distances. However, these studies do not define the specific targets of HIF‐binding sites and do not reveal how induction of HIF affects chromatin conformation over distantly connected functional elements. To address these questions, we deployed a recently developed chromosome conformation assay that enables simultaneous high‐resolution analyses from multiple viewpoints. These assays defined specific long‐range interactions between intergenic HIF‐binding regions and one or more promoters of hypoxia‐inducible genes, revealing the existence of multiple enhancer–promoter, promoter–enhancer, and enhancer–enhancer interactions. However, neither short‐term activation of HIF by hypoxia, nor long‐term stabilization of HIF in von Hippel–Lindau (VHL)‐defective cells greatly alters these interactions, indicating that at least under these conditions, HIF can operate on preexisting patterns of chromatin–chromatin interactions that define potential transcriptional targets and permit rapid gene activation by hypoxic stress.
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spelling pubmed-50483712016-11-14 Capture‐C reveals preformed chromatin interactions between HIF‐binding sites and distant promoters Platt, James L Salama, Rafik Smythies, James Choudhry, Hani Davies, James OJ Hughes, Jim R Ratcliffe, Peter J Mole, David R EMBO Rep Scientific Reports Hypoxia‐inducible factor (HIF) directs an extensive transcriptional cascade that transduces numerous adaptive responses to hypoxia. Pan‐genomic analyses, using chromatin immunoprecipitation and transcript profiling, have revealed large numbers of HIF‐binding sites that are generally associated with hypoxia‐inducible transcripts, even over long chromosomal distances. However, these studies do not define the specific targets of HIF‐binding sites and do not reveal how induction of HIF affects chromatin conformation over distantly connected functional elements. To address these questions, we deployed a recently developed chromosome conformation assay that enables simultaneous high‐resolution analyses from multiple viewpoints. These assays defined specific long‐range interactions between intergenic HIF‐binding regions and one or more promoters of hypoxia‐inducible genes, revealing the existence of multiple enhancer–promoter, promoter–enhancer, and enhancer–enhancer interactions. However, neither short‐term activation of HIF by hypoxia, nor long‐term stabilization of HIF in von Hippel–Lindau (VHL)‐defective cells greatly alters these interactions, indicating that at least under these conditions, HIF can operate on preexisting patterns of chromatin–chromatin interactions that define potential transcriptional targets and permit rapid gene activation by hypoxic stress. John Wiley and Sons Inc. 2016-08-09 2016-10 /pmc/articles/PMC5048371/ /pubmed/27506891 http://dx.doi.org/10.15252/embr.201642198 Text en © 2016 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Scientific Reports
Platt, James L
Salama, Rafik
Smythies, James
Choudhry, Hani
Davies, James OJ
Hughes, Jim R
Ratcliffe, Peter J
Mole, David R
Capture‐C reveals preformed chromatin interactions between HIF‐binding sites and distant promoters
title Capture‐C reveals preformed chromatin interactions between HIF‐binding sites and distant promoters
title_full Capture‐C reveals preformed chromatin interactions between HIF‐binding sites and distant promoters
title_fullStr Capture‐C reveals preformed chromatin interactions between HIF‐binding sites and distant promoters
title_full_unstemmed Capture‐C reveals preformed chromatin interactions between HIF‐binding sites and distant promoters
title_short Capture‐C reveals preformed chromatin interactions between HIF‐binding sites and distant promoters
title_sort capture‐c reveals preformed chromatin interactions between hif‐binding sites and distant promoters
topic Scientific Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048371/
https://www.ncbi.nlm.nih.gov/pubmed/27506891
http://dx.doi.org/10.15252/embr.201642198
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