The 13,130 differentially methylated cytosines (DMCs; Pâ<â0.05) that were located within a promoter or untranslated regions (3' and 5'). (XLSX 2880 kb

Dawn Coletta (3560534)

Elena De Filippis (2993133)

Gabriel Shaibi (3560525)

Joon Kim (510697)

Latoya Campbell (3560537)

Lawrence Mandarino (3505169)

Lori Roust (3560531)

Richard Coletta (3560528)

Samantha Day (3560522)

Tonya Benjamin (3560519)

Valentin Dinu (801175)

Clinical Epigenetics

PubMed

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Additional file 1: Table S1. of Next-generation sequencing methylation profiling of subjects with obesity identifies novel gene changes

Samantha E. Day

Richard L. Coletta

Joon Young Kim

Latoya E. Campbell

Tonya R. Benjamin

Lori R. Roust

Elena A. De Filippis

Valentin Dinu

Gabriel Q. Shaibi

Lawrence J. Mandarino

Dawn K. Coletta

Crossref

Next-generation sequencing methylation profiling of subjects with obesity identifies novel gene changes

Background: Obesity is a metabolic disease caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are incompletely understood. The aim of our study was to investigate the role of skeletal muscle DNA methylation in combination with transcriptomic changes in obesity. Results: Muscle biopsies were obtained basally from lean (n = 12; BMI = 23.4 +/- 0.7 kg/m(2)) and obese (n = 10; BMI = 32.9 +/- 0.7 kg/m(2)) participants in combination with euglycemic-hyperinsulinemic clamps to assess insulin sensitivity. We performed reduced representation bisulfite sequencing (RRBS) next-generation methylation and microarray analyses on DNA and RNA isolated from vastus lateralis muscle biopsies. There were 13,130 differentially methylated cytosines (DMC; uncorrected P < 0.05) that were altered in the promoter and untranslated (5' and 3'UTR) regions in the obese versus lean analysis. Microarray analysis revealed 99 probes that were significantly (corrected P < 0.05) altered. Of these, 12 genes (encompassing 22 methylation sites) demonstrated a negative relationship between gene expression and DNA methylation. Specifically, sorbin and SH3 domain containing 3 (SORBS3) which codes for the adapter protein vinexin was significantly decreased in gene expression (fold change -1.9) and had nine DMCs that were significantly increased in methylation in obesity (methylation differences ranged from 5.0 to 24.4 %). Moreover, differentially methylated region (DMR) analysis identified a region in the 5' UTR (Chr. 8: 22,423,530-22,423,569) of SORBS3 that was increased in methylation by 11.2 % in the obese group. The negative relationship observed between DNA methylation and gene expression for SORBS3 was validated by a site-specific sequencing approach, pyrosequencing, and qRT-PCR. Additionally, we performed transcription factor binding analysis and identified a number of transcription factors whose binding to the differentially methylated sites or region may contribute to obesity. Conclusions: These results demonstrate that obesity alters the epigenome through DNA methylation and highlights novel transcriptomic changes in SORBS3 in skeletal muscle.National Institutes of Health [R01DK094013]Open Access JournalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu

Day, Samantha E.

Coletta, Richard L.

Kim, Joon Young

Campbell, Latoya E.

Benjamin, Tonya R.

Roust, Lori R.

De Filippis, Elena A.

Dinu, Valentin

Shaibi, Gabriel Q.

Mandarino, Lawrence J.

Coletta, Dawn K.

The University of Arizona

http://dx.doi.org/10.1186/s13148-016-0246-x

Additional file 1: Table S1. of Next-generation sequencing methylation profiling of subjects with obesity identifies novel gene changes

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