Faculty Collaboration Database

Enhancer transcribed RNAs arise from hypomethylated, Tet-occupied genomic regions. Epigenetics 2013 Dec;8(12):1303-20

Date

10/19/2013

Pubmed ID

24135681

Pubmed Central ID

PMC3933491

DOI

10.4161/epi.26597

Scopus ID

2-s2.0-84888790012 (requires institutional sign-in at Scopus site)   52 Citations

Abstract

Enhancers are cis-acting elements capable of regulating transcription in a distance and orientation-independent manner. A subset of enhancers are occupied by RNA polymerase II (RNAP II) and transcribed to produce long non-coding RNAs termed eRNAs. We thoroughly investigated the association between eRNA productivity and various chromatin marks and transcriptional regulators in mouse embryonic stem cells (ESCs) through an integrative approach. We found that eRNA-producing enhancers exhibited elevated levels of the active mark H3K27Ac, decreased DNA methylation, and enrichment for the DNA hydroxylase Tet1. Many eRNA-producing enhancers have recently been characterized as "super-enhancers," suggesting an important role in the maintenance of pluripotency. Using experimental methods, we focally investigated a well-characterized enhancer linked to the Nanog locus and confirmed its exclusive eRNA productivity in ESCs. We further demonstrate that the binding of Sall4 and Tet family proteins were required for eRNA productivity at this locus. Collectively, we demonstrate that Tet1 binding and DNA hypomethylation are hallmarks of eRNA production.

Author List

Pulakanti K, Pinello L, Stelloh C, Blinka S, Allred J, Milanovich S, Kiblawi S, Peterson J, Wang A, Yuan GC, Rao S

Author

Sridhar Rao MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Line
DNA (Cytosine-5-)-Methyltransferases
DNA Methylation
DNA-Binding Proteins
Embryonic Stem Cells
Enhancer Elements, Genetic
Homeodomain Proteins
Mice
NIH 3T3 Cells
Nanog Homeobox Protein
Promoter Regions, Genetic
Proto-Oncogene Proteins
RNA
Regulatory Elements, Transcriptional
Transcription, Genetic