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Negative Regulation of Enhancer‐Associated RNA in Macrophages
Author(s) -
Lam Michael T,
Cho Han,
Heinz Sven,
Benner Christopher,
Kaikkonen Minna U,
Tanaka-Oishi Yumiko,
Kosaka Mika,
Lee Cindy,
Evans Ronald M,
Glass Christopher K
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.912.1
Subject(s) - enhancer , enhancer rnas , biology , chromatin immunoprecipitation , transcription (linguistics) , rna polymerase ii , gene , rna , chromatin , long non coding rna , non coding rna , repressor , gene expression , genetics , microbiology and biotechnology , promoter , linguistics , philosophy
Recent discoveries of genome‐wide transcription at non‐coding regions suggest an unrecognized role of non‐coding RNAs. One class of these non‐coding RNAs is transcribed from cell‐type specific enhancer elements (eRNA). Here we show how transcription of eRNAs is negatively regulated by Rev‐Erb α and β, a subclass of the nuclear receptor family characterized as dedicated transcriptional repressors. Genome‐wide localization of Rev‐Erb α and β in macrophages by chromatin‐immunoprecipitation couple with sequencing showed that 70% of their binding sites are located in enhancer elements distal to protein coding genes. Approximately 55% of these distal regions are enriched for RNA Polymerase II. To test whether these enhancer elements express RNAs, we performed global run‐on sequencing with confirmation using RT‐PCR and detected nascent RNA transcripts at Rev‐Erb bound enhancers. Transcription of eRNA is de‐repressed in Rev‐ Erb deficient macrophages, whereas constitutive expression of Rev‐Erb represses eRNA transcription. Moreover, changes in eRNA expression are positively correlated to changes in expression of nearby protein coding genes. These findings suggest a mechanism whereby Rev‐Erb regulates gene expression by repressing eRNA from distal enhancer elements. Grant Funding Source : NIH