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Orphan CpG islands amplify poised enhancer regulatory activity and determine target gene responsiveness
CpG islands (CGIs) represent a widespread feature of vertebrate genomes, being associated with ~70% of all gene promoters. CGIs control transcription initiation by conferring nearby promoters with unique chromatin properties. In addition, there are thousands of distal or orphan CGIs (oCGIs) whose fu...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611182/ https://www.ncbi.nlm.nih.gov/pubmed/34183853 http://dx.doi.org/10.1038/s41588-021-00888-x |
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author | Pachano, Tomas Sánchez-Gaya, Víctor Ealo, Thais Mariner-Faulí, Maria Bleckwehl, Tore Asenjo, Helena G. Respuela, Patricia Cruz-Molina, Sara Martín, María Muñoz-San Haro, Endika van IJcken, Wilfred F. J. Landeira, David Rada-Iglesias, Alvaro |
author_facet | Pachano, Tomas Sánchez-Gaya, Víctor Ealo, Thais Mariner-Faulí, Maria Bleckwehl, Tore Asenjo, Helena G. Respuela, Patricia Cruz-Molina, Sara Martín, María Muñoz-San Haro, Endika van IJcken, Wilfred F. J. Landeira, David Rada-Iglesias, Alvaro |
author_sort | Pachano, Tomas |
collection | PubMed |
description | CpG islands (CGIs) represent a widespread feature of vertebrate genomes, being associated with ~70% of all gene promoters. CGIs control transcription initiation by conferring nearby promoters with unique chromatin properties. In addition, there are thousands of distal or orphan CGIs (oCGIs) whose functional relevance is barely known. Here we show that oCGIs are an essential component of poised enhancers (PEs) that augment their long-range regulatory activity and control the responsiveness of their target genes. Using a knock-in strategy in mouse embryonic stem cells (ESCs), we introduced PEs with or without oCGIs within topologically associating domains (TADs) harboring genes with different types of promoters. Analysis of the resulting cell lines revealed that oCGIs act as tethering elements that promote the physical and functional communication between PEs and distally located genes, particularly those with large CGI clusters in their promoters. Therefore, by acting as genetic determinants of gene-enhancer compatibility, CGIs can contribute to gene expression control under both physiological and potentially pathological conditions. |
format | Online Article Text |
id | pubmed-7611182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-76111822021-12-28 Orphan CpG islands amplify poised enhancer regulatory activity and determine target gene responsiveness Pachano, Tomas Sánchez-Gaya, Víctor Ealo, Thais Mariner-Faulí, Maria Bleckwehl, Tore Asenjo, Helena G. Respuela, Patricia Cruz-Molina, Sara Martín, María Muñoz-San Haro, Endika van IJcken, Wilfred F. J. Landeira, David Rada-Iglesias, Alvaro Nat Genet Article CpG islands (CGIs) represent a widespread feature of vertebrate genomes, being associated with ~70% of all gene promoters. CGIs control transcription initiation by conferring nearby promoters with unique chromatin properties. In addition, there are thousands of distal or orphan CGIs (oCGIs) whose functional relevance is barely known. Here we show that oCGIs are an essential component of poised enhancers (PEs) that augment their long-range regulatory activity and control the responsiveness of their target genes. Using a knock-in strategy in mouse embryonic stem cells (ESCs), we introduced PEs with or without oCGIs within topologically associating domains (TADs) harboring genes with different types of promoters. Analysis of the resulting cell lines revealed that oCGIs act as tethering elements that promote the physical and functional communication between PEs and distally located genes, particularly those with large CGI clusters in their promoters. Therefore, by acting as genetic determinants of gene-enhancer compatibility, CGIs can contribute to gene expression control under both physiological and potentially pathological conditions. 2021-07-01 2021-06-28 /pmc/articles/PMC7611182/ /pubmed/34183853 http://dx.doi.org/10.1038/s41588-021-00888-x Text en http://www.nature.com/authors/editorial_policies/license.html#termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Pachano, Tomas Sánchez-Gaya, Víctor Ealo, Thais Mariner-Faulí, Maria Bleckwehl, Tore Asenjo, Helena G. Respuela, Patricia Cruz-Molina, Sara Martín, María Muñoz-San Haro, Endika van IJcken, Wilfred F. J. Landeira, David Rada-Iglesias, Alvaro Orphan CpG islands amplify poised enhancer regulatory activity and determine target gene responsiveness |
title | Orphan CpG islands amplify poised enhancer regulatory activity and determine target gene responsiveness |
title_full | Orphan CpG islands amplify poised enhancer regulatory activity and determine target gene responsiveness |
title_fullStr | Orphan CpG islands amplify poised enhancer regulatory activity and determine target gene responsiveness |
title_full_unstemmed | Orphan CpG islands amplify poised enhancer regulatory activity and determine target gene responsiveness |
title_short | Orphan CpG islands amplify poised enhancer regulatory activity and determine target gene responsiveness |
title_sort | orphan cpg islands amplify poised enhancer regulatory activity and determine target gene responsiveness |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611182/ https://www.ncbi.nlm.nih.gov/pubmed/34183853 http://dx.doi.org/10.1038/s41588-021-00888-x |
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