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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
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.
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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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