Pervasive and CpG-dependent promoter-like characteristics of transcribed enhancers.

Publication Type Academic Article
Authors Steinhaus R, Gonzalez T, Seelow D, Robinson P
Journal Nucleic Acids Res
Volume 48
Issue 10
Pagination 5306-5317
Date Published 06/04/2020
ISSN 1362-4962
Keywords CpG Islands, Enhancer Elements, Genetic, Promoter Regions, Genetic, Transcription, Genetic
Abstract The temporal and spatial expression of genes is controlled by promoters and enhancers. Findings obtained over the last decade that not only promoters but also enhancers are characterized by bidirectional, divergent transcription have challenged the traditional notion that promoters and enhancers represent distinct classes of regulatory elements. Over half of human promoters are associated with CpG islands (CGIs), relatively CpG-rich stretches of generally several hundred nucleotides that are often associated with housekeeping genes. Only about 6% of transcribed enhancers defined by CAGE-tag analysis are associated with CGIs. Here, we present an analysis of enhancer and promoter characteristics and relate them to the presence or absence of CGIs. We show that transcribed enhancers share a number of CGI-dependent characteristics with promoters, including statistically significant local overrepresentation of core promoter elements. CGI-associated enhancers are longer, display higher directionality of transcription, greater expression, a lesser degree of tissue specificity, and a higher frequency of transcription-factor binding events than non-CGI-associated enhancers. Genes putatively regulated by CGI-associated enhancers are enriched for transcription regulator activity. Our findings show that CGI-associated transcribed enhancers display a series of characteristics related to sequence, expression and function that distinguish them from enhancers not associated with CGIs.
DOI 10.1093/nar/gkaa223
PubMed ID 32338759
PubMed Central ID PMC7261191
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