Pachano, Tomas, Sanchez-Gaya, Victor, Ealo, Thais, Mariner-Fauli, Maria, Bleckwehl, Tore, Asenjo, Helena G., Respuela, Patricia, Cruz-Molina, Sara, Munoz-San Martin, Maria, Haro, Endika, van IJcken, Wilfred F. J., Landeira, David ORCID: 0000-0002-3267-454X and Rada-Iglesias, Alvaro ORCID: 0000-0001-7137-1341 (2021). Orphan CpG islands amplify poised enhancer regulatory activity and determine target gene responsiveness. Nature Genet., 53 (7). S. 1036 - 1074. BERLIN: NATURE RESEARCH. ISSN 1546-1718

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Abstract

CpG islands (CGIs) represent a widespread feature of vertebrate genomes, being associated with similar to 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 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, we introduced poised enhancers with or without oCGIs within topologically associating domains 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 poised enhancers 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Pachano, TomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanchez-Gaya, VictorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ealo, ThaisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mariner-Fauli, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bleckwehl, ToreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Asenjo, Helena G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Respuela, PatriciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cruz-Molina, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Munoz-San Martin, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haro, EndikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van IJcken, Wilfred F. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Landeira, DavidUNSPECIFIEDorcid.org/0000-0002-3267-454XUNSPECIFIED
Rada-Iglesias, AlvaroUNSPECIFIEDorcid.org/0000-0001-7137-1341UNSPECIFIED
URN: urn:nbn:de:hbz:38-596041
DOI: 10.1038/s41588-021-00888-x
Journal or Publication Title: Nature Genet.
Volume: 53
Number: 7
Page Range: S. 1036 - 1074
Date: 2021
Publisher: NATURE RESEARCH
Place of Publication: BERLIN
ISSN: 1546-1718
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PROMOTER SPECIFICITY; DNA METHYLATION; TRANSCRIPTION FACTORS; ASSOCIATING DOMAINS; POLYCOMB PROTEINS; PRC2 RECRUITMENT; CHROMATIN; MOUSE; EXPRESSION; ELEMENTSMultiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59604

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