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Mol Cell. 2018 Jul 5;71(1):129-141.e8. doi: 10.1016/j.molcel.2018.06.008.

A Muscle-Specific Enhancer RNA Mediates Cohesin Recruitment and Regulates Transcription In trans.

Author information

1
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 20892, USA.
2
High-Throughput Sequencing Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 20892, USA.
3
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
4
Biodata Mining and Discovery Section, NIAMS, NIH, Bethesda, MD 20892, USA.
5
Translational Immunology Section, NIAMS, NIH, Bethesda, MD 20892, USA.
6
Light Imaging Section, NIAMS, NIH, Bethesda, MD 20892, USA.
7
Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
8
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 20892, USA. Electronic address: sartorev@mail.nih.gov.

Abstract

The enhancer regions of the myogenic master regulator MyoD give rise to at least two enhancer RNAs. Core enhancer eRNA (CEeRNA) regulates transcription of the adjacent MyoD gene, whereas DRReRNA affects expression of Myogenin in trans. We found that DRReRNA is recruited at the Myogenin locus, where it colocalizes with Myogenin nascent transcripts. DRReRNA associates with the cohesin complex, and this association correlates with its transactivating properties. Despite being expressed in undifferentiated cells, cohesin is not loaded on Myogenin until the cells start expressing DRReRNA, which is then required for cohesin chromatin recruitment and maintenance. Functionally, depletion of either cohesin or DRReRNA reduces chromatin accessibility, prevents Myogenin activation, and hinders muscle cell differentiation. Thus, DRReRNA ensures spatially appropriate cohesin loading in trans to regulate gene expression.

KEYWORDS:

Myogenin; cohesin; enhancer RNA; muscle gene transcription; non-coding RNA

PMID:
29979962
PMCID:
PMC6082425
[Available on 2019-07-05]
DOI:
10.1016/j.molcel.2018.06.008

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