Epigenetics of the myotonic dystrophy-associated DMPK gene neighborhood. (January 2016)

• Record Type: Journal Article
• Authors: Buckley, Lauren; Lacey, Michelle; Ehrlich, Melanie
• Is Part Of: Epigenomics. Volume 8:Number 1(2016)
• Page Start: 13
• Page End: 31
• Publication Date: 2016-01
• Subjects: alternative promoters -- CTCF -- DNA methylation -- enhancers -- G-quadruplex -- histone modification -- muscle -- myotonic dystrophy -- sperm DNA -- testis; Epigenesis -- Periodicals; Genomics -- Periodicals; Chromatin -- Periodicals; DNA -- Periodicals; 572.87
• DOI: 10.2217/epi.15.104
• Languages: English
• ISSNs: 1750-1911

Abstract

Aim: Identify epigenetic marks in the vicinity of DMPK (linked to myotonic dystrophy, DM1) that help explain tissue-specific differences in its expression.Materials & methods: At DMPK and its flanking genes ( DMWD, SIX5, BHMG1 and RSPH6A ), we analyzed many epigenetic and transcription profiles from myoblasts, myotubes, skeletal muscle, heart and 30 nonmuscle samples.Results: In the DMPK gene neighborhood, muscle-associated DNA hypermethylation and hypomethylation, enhancer chromatin, and CTCF binding were seen. Myogenic DMPK hypermethylation correlated with high expression and decreased alternative promoter usage. Testis/sperm hypomethylation of BHMG1 and RSPH6A was associated with testis-specific expression. G-quadruplex (G4) motifs and sperm-specific hypomethylation were found near the DM1-linked CTG repeats within DMPK .Conclusion: Tissue-specific epigenetic features in DMPK and neighboring genes help regulate its expression. G4 motifs in DMPK DNA and RNA might contribute to DM1 pathology.