Molecular Profiling of DNA Methylation and Alternative Splicing of Genes in Skeletal Muscle of Obese Rabbits

Abstract

DNA methylation and the alternative splicing of precursor messenger RNAs (pre-mRNAs) are two important genetic modification mechanisms. However, both are currently uncharacterized in the muscle metabolism of rabbits. Thus, we constructed the Tianfu black rabbit obesity model (obese rabbits fed with a 10% high-fat diet and control rabbits from 35 days to 70 days) and collected the skeletal muscle samples from the two groups for Genome methylation sequencing and RNA sequencing. DNA methylation data showed that the promoter regions of 599 genes and gene body region of 2522 genes had significantly differential methylation rates between the two groups, of which 288 genes had differential methylation rates in promoter and gene body regions. Analysis of alternative splicing showed 555 genes involved in exon skipping (ES) patterns, and 15 genes existed in differential methylation regions. Network analysis showed that 20 hub genes were associated with ubiquitinated protein degradation, muscle development pathways, and skeletal muscle energy metabolism. Our findings suggest that the two types of genetic modification have potential regulatory effects on skeletal muscle development and provide a basis for further mechanistic studies in the rabbit.

Punicalagin protects against impaired skeletal muscle function in high-fat-diet-induced obese mice by regulating TET2

“…, Titin and Pgc1α ) and increasing the risk of deficiency in skeletal muscle mass and amyosthenia. 8,45,46 Consequently, enhancing the DNA demethylation capacity of skeletal muscles can help to restore the skeletal muscle function. The levels of 5hmC and 5fC, which are intermediate products obtained by the repeated oxidation of 5mC by TETs, correspond to the degree of demethylation.…”

“…15,44,45 Clinical and experimental data suggest that a HFD can lead to skeletal muscle hypermethylation, in turn suppressing the expression of numerous genes essential for skeletal muscle growth (e.g., Titin and Pgc1α) and increasing the risk of deficiency in skeletal muscle mass and amyosthenia. 8,45,46 Consequently, enhancing the DNA demethylation capacity of skeletal muscles can help to restore the skeletal muscle function. The levels of 5hmC and 5fC, which are intermediate products obtained by the repeated oxidation of 5mC by TETs, correspond to the degree of demethylation.…”

Preliminary Results about Lamb Meat Tenderness Based on the Study of Novel Isoforms and Alternative Splicing Regulation Pathways Using Iso-seq, RNA-seq and CTCF ChIP-seq Data

“…In a cattle study, the ANKRD23-202 mRNA isoform, which is a splice form of the ANKRD, was defined as a DEI between the tough group and the tender group [49]. The result of a rabbit study suggested that ANKRD23 methylated in promoter and gene body regions is associated with exon skipping alternative splicing in the skeletal muscle [51]. Previous results suggest that CTCF could regulate alternative splicing by controlling DNA methylation [52][53][54].…”