Table_1_The Landscape of DNA Methylation Associated With the Transcriptomic Network of Intramuscular Adipocytes Generates Insight Into Intramuscular Fat Deposition in Chicken.DOCX

Intramuscular fat (IMF), which regulated by genetics, nutrition and environment is an important factor that influencing meat quality. Up to now, the epigenetic regulation mechanism underlying poultry IMF deposition remains poorly understood. Here, we focused on the DNA methylation, which usually regulate genes in transcription level. To look into the essential role of DNA methylation on the IMF deposition, chicken intramuscular preadipocytes were isolated and cultured in vitro, and a model of intramuscular adipocyte differentiation was constructed. Combined the whole genome bisulfite sequencing (WGBS) and RNA-Seq technologies, we identified several methylated genes, which mainly affecting fatty acid metabolism and muscle development. Furthermore, we reported that DNA methylation regulate intramuscular adipogenesis by regulating the genes, such as collagen, type VI, alpha 1 (COL6A1) thus affecting IMF deposition. Overexpression of COL6A1 increases the lipid droplet and inhibits cell proliferation by regulating CHAD and CAMK2 in intramuscular adipocytes, while knockdown of COL6A1 shows the opposite effect. Taken together, our results reveal that DNA methylation plays an important role in poultry IMF deposition.

肌内脂肪（Intramuscular fat, IMF）受遗传、营养与环境共同调控，是影响肉质的关键因素。截至目前，禽类肌内脂肪沉积的表观遗传调控机制仍未得到充分阐释。本研究聚焦于通常在转录水平调控基因表达的DNA甲基化（DNA methylation）。为探究DNA甲基化在肌内脂肪沉积中的核心作用，我们分离并体外培养了鸡肌内前体脂肪细胞，构建了肌内脂肪细胞分化模型。结合全基因组亚硫酸氢盐测序（Whole Genome Bisulfite Sequencing, WGBS）与RNA-Seq技术，本研究鉴定出多个主要参与脂肪酸代谢及肌肉发育的甲基化基因。此外，本研究发现DNA甲基化可通过调控Ⅵ型胶原α1（COL6A1）等基因的表达调控肌内脂肪生成，进而影响肌内脂肪沉积。在肌内脂肪细胞中，过表达COL6A1可通过调控CHAD与CAMK2的表达增加脂滴数量并抑制细胞增殖，而敲低COL6A1则会产生相反的效应。综上，本研究结果表明DNA甲基化在禽类肌内脂肪沉积中发挥重要调控作用。