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Biology 2014, 3(2), 426-451; doi:10.3390/biology3020426

Myogenic Differential Methylation: Diverse Associations with Chromatin Structure

1
Center for Bioinformatics and Genomics, New Orleans, LA 70112, USA
2
Tulane Cancer Center, Tulane University Health Sciences Center, New Orleans, LA 70112, USA
3
Department of Mathematics, Tulane University, New Orleans, LA 70112, USA
4
Program in Human Genetics Program, Tulane University, New Orleans, LA 70112, USA
*
Author to whom correspondence should be addressed.
Received: 18 April 2014 / Revised: 21 May 2014 / Accepted: 21 May 2014 / Published: 19 June 2014
(This article belongs to the Special Issue DNA Methylation)
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Abstract

Employing a new algorithm for identifying differentially methylated regions (DMRs) from reduced representation bisulfite sequencing profiles, we identified 1972 hypermethylated and 3250 hypomethylated myogenic DMRs in a comparison of myoblasts (Mb) and myotubes (Mt) with 16 types of nonmuscle cell cultures. DMRs co-localized with a variety of chromatin structures, as deduced from ENCODE whole-genome profiles. Myogenic hypomethylation was highly associated with both weak and strong enhancer-type chromatin, while hypermethylation was infrequently associated with enhancer-type chromatin. Both myogenic hypermethylation and hypomethylation often overlapped weak transcription-type chromatin and Polycomb-repressed-type chromatin. For representative genes, we illustrate relationships between DNA methylation, the local chromatin state, DNaseI hypersensitivity, and gene expression. For example, MARVELD2 exhibited myogenic hypermethylation in transcription-type chromatin that overlapped a silenced promoter in Mb and Mt while TEAD4 had myogenic hypomethylation in intronic subregions displaying enhancer-type or transcription-type chromatin in these cells. For LSP1, alternative promoter usage and active promoter-type chromatin were linked to highly specific myogenic or lymphogenic hypomethylated DMRs. Lastly, despite its myogenesis-associated expression, TBX15 had multiple hypermethylated myogenic DMRs framing its promoter region. This could help explain why TBX15 was previously reported to be underexpressed and, unexpectedly, its promoter undermethylated in placentas exhibiting vascular intrauterine growth restriction. View Full-Text
Keywords: DNA methylation; histone modification; myoblasts; DNaseI hypersensitivity; differentiation; enhancers; promoters; Polycomb group repression; muscle DNA methylation; histone modification; myoblasts; DNaseI hypersensitivity; differentiation; enhancers; promoters; Polycomb group repression; muscle
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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Chandra, S.; Baribault, C.; Lacey, M.; Ehrlich, M. Myogenic Differential Methylation: Diverse Associations with Chromatin Structure. Biology 2014, 3, 426-451.

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