Myogenic Differential Methylation: Diverse Associations with Chromatin Structure
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 c...
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-06-01
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| Series: | Biology |
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| Online Access: | http://www.mdpi.com/2079-7737/3/2/426 |
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| author | Sruti Chandra Carl Baribault Michelle Lacey Melanie Ehrlich |
| author_facet | Sruti Chandra Carl Baribault Michelle Lacey Melanie Ehrlich |
| author_sort | Sruti Chandra |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T11:12:48Z |
| format | Article |
| id | doaj.art-a0289121569f4b7283284e3662ff451f |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-12T11:12:48Z |
| publishDate | 2014-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-a0289121569f4b7283284e3662ff451f2023-09-02T02:40:54ZengMDPI AGBiology2079-77372014-06-013242645110.3390/biology3020426biology3020426Myogenic Differential Methylation: Diverse Associations with Chromatin StructureSruti Chandra0Carl Baribault1Michelle Lacey2Melanie Ehrlich3Center for Bioinformatics and Genomics, New Orleans, LA 70112, USATulane Cancer Center, Tulane University Health Sciences Center, New Orleans, LA 70112, USATulane Cancer Center, Tulane University Health Sciences Center, New Orleans, LA 70112, USACenter for Bioinformatics and Genomics, New Orleans, LA 70112, USAEmploying 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.http://www.mdpi.com/2079-7737/3/2/426DNA methylationhistone modificationmyoblastsDNaseI hypersensitivitydifferentiationenhancerspromotersPolycomb group repressionmuscle |
| spellingShingle | Sruti Chandra Carl Baribault Michelle Lacey Melanie Ehrlich Myogenic Differential Methylation: Diverse Associations with Chromatin Structure Biology DNA methylation histone modification myoblasts DNaseI hypersensitivity differentiation enhancers promoters Polycomb group repression muscle |
| title | Myogenic Differential Methylation: Diverse Associations with Chromatin Structure |
| title_full | Myogenic Differential Methylation: Diverse Associations with Chromatin Structure |
| title_fullStr | Myogenic Differential Methylation: Diverse Associations with Chromatin Structure |
| title_full_unstemmed | Myogenic Differential Methylation: Diverse Associations with Chromatin Structure |
| title_short | Myogenic Differential Methylation: Diverse Associations with Chromatin Structure |
| title_sort | myogenic differential methylation diverse associations with chromatin structure |
| topic | DNA methylation histone modification myoblasts DNaseI hypersensitivity differentiation enhancers promoters Polycomb group repression muscle |
| url | http://www.mdpi.com/2079-7737/3/2/426 |
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