Epigenetic Modifications of the PGC-1α Promoter during Exercise Induced Expression in Mice

Authors

Timothy L. Lochmann, Virginia Commonwealth UniversityFollow
Ravindar R. Thomas, Virginia Commonwealth UniversityFollow
James P. Bennett, Virginia Commonwealth UniversityFollow
Shirley M. Taylor, Virginia Commonwealth UniversityFollow

Document Type

Article

Original Publication Date

2015

Journal/Book/Conference Title

PLoS ONE

Volume

10

Issue

6

DOI of Original Publication

10.1371/journal.pone.0129647

Comments

Originally published at http://dx.doi.org/10.1371/journal.pone.0129647

Date of Submission

November 2015

Abstract

The transcriptional coactivator, PGC-1α, is known for its role in mitochondrial biogenesis. Although originally thought to exist as a single protein isoform, recent studies have identified additional promoters which produce multiple mRNA transcripts. One of these promoters (promoter B), approximately 13.7kb upstream of the canonical PGC-1α promoter (promoter A), yields alternative transcripts present at levels much lower than the canonical PGC-1α mRNA transcript. In skeletal muscle, exercise resulted in a substantial, rapid increase of mRNA of these alternative PGC-1α transcripts. Although the β2-adrenergic receptor was identified as a signaling pathway that activates transcription from PGC-1α promoter B, it is not yet known what molecular changes occur to facilitate PGC-1α promoter B activation following exercise. We sought to determine whether epigenetic modifications were involved in this exercise response in mouse skeletal muscle. We found that DNA hydroxymethylation correlated to increased basal mRNA levels from PGC-1α promoter A, but that DNA methylation appeared to play no role in the exercise-induced activation of PGC-1α promoter B. The level of the activating histone mark H3K4me3 increased with exercise 2–4 fold across PGC-1α promoter B, but remained unaltered past the canonical PGC-1α transcriptional start site. Together, these data show that epigenetic modifications partially explain exercise-induced changes in the skeletal muscle mRNA levels of PGC-1α isoforms.

Rights

Lochmann, T. L., Thomas, R. R., & Bennett Jr., J. P., et al. Epigenetic Modifications of the PGC-1α Promoter during Exercise Induced Expression in Mice. PLoS ONE, 10, e0129647. Copyright © 2015 Lochmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Is Part Of

VCU Massey Cancer Center Publications