Epigenetics of the Myotonic Dystrophy-Associated DMPK gene neighborhood

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.

Keywords::

• alternative promoters
• CTCF
• DNA methylation
• enhancers
• G-quadruplex
• histone modification
• muscle
• myotonic dystrophy
• sperm DNA
• testis

To view the supplementary data that accompany this paperplease visit thejournal website at: www.tandfonline.com/doi/full/10.2217/epi.15.104

Acknowledgements

The authors thank M Badoo and the Tulane Cancer Center (COBRE grant NIGMS P20GM103518) for help with the Cufflinks analysis of the ENCODE RNA-seq data.

Financial & competing interests disclosure

This research was supported in part by a grant from the NIH to M Ehrlich (NS04885). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This research was supported in part by a grant from the NIH to M Ehrlich (NS04885). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.