College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, Gansu, China.
Key Laboratory of Pig Industry Sciences (Ministry of Agriculture), Chongqing Academy of Animal Science, Chongqing, China.
PeerJ. 2022 May 24;10:e13250. doi: 10.7717/peerj.13250. eCollection 2022.
Fat accumulation in visceral adipose tissue (VAT) confers increased risk for metabolic disorders of obesity, whereas accumulation of subcutaneous adipose tissue (SAT) is associated with lower risk and may be protective. Previous studies have shed light on the gene expression profile differences between SAT and VAT; however, the chromatin accessibility landscape differences and how the cis-regulatory elements govern gene expression changes between SAT and VAT are unknown.
Pig were used to characterize the differences in chromatin accessibility between the two adipose depots-derived stromal vascular fractions (SVFs) using DNase-sequencing (DNase-seq). Using integrated data from DNase-seq, H3K27ac ChIP-sequencing (ChIP-seq), and RNA-sequencing (RNA-seq), we investigated how the regulatory locus complexity regulated gene expression changes between SAT and VAT and the possible impact that these changes may have on the different biological functions of these two adipose depots.
SVFs form SAT and VAT (S-SVF and V-SVF) have differential chromatin accessibility landscapes. The differential DNase I hypersensitive site (DHS)-associated genes, which indicate dynamic chromatin accessibility, were mainly involved in metabolic processes and inflammatory responses. Additionally, the Krüppel-like factor family of transcription factors were enriched in the differential DHSs. Furthermore, the chromatin accessibility data were highly associated with differential gene expression as indicated using H3K27ac ChIP-seq and RNA-seq data, supporting the validity of the differential gene expression determined using DNase-seq. Moreover, by combining epigenetic and transcriptomic data, we identified two candidate genes, and , could be crucial to regulate distinct metabolic and inflammatory characteristics between SAT and VAT. Together, these results uncovered differences in the transcription regulatory network and enriched the mechanistic understanding of the different biological functions between SAT and VAT.
内脏脂肪组织（VAT）中的脂肪堆积会增加肥胖相关代谢紊乱的风险，而皮下脂肪组织（SAT）的堆积则与较低的风险相关，并且可能具有保护作用。先前的研究已经揭示了 SAT 和 VAT 之间基因表达谱的差异；然而，SAT 和 VAT 之间染色质可及性差异的调控元件以及顺式调控元件如何调控基因表达变化尚不清楚。
利用 DNase-seq 技术对猪 SAT 和 VAT 来源的基质血管部分（SVF）进行染色质可及性差异分析。利用 DNase-seq、H3K27ac ChIP-seq 和 RNA-seq 的整合数据，我们研究了调控区域复杂性如何调控 SAT 和 VAT 之间的基因表达变化，以及这些变化可能对这两个脂肪组织不同生物学功能的可能影响。
SVF 形成的 SAT 和 VAT（S-SVF 和 V-SVF）具有不同的染色质可及性图谱。差异的 DNase I 超敏位点（DHS）相关基因，指示动态染色质可及性，主要参与代谢过程和炎症反应。此外，转录因子 Krüppel 样因子家族在差异 DHS 中富集。此外，染色质可及性数据与使用 H3K27ac ChIP-seq 和 RNA-seq 数据确定的差异基因表达高度相关，支持使用 DNase-seq 确定的差异基因表达的有效性。此外，通过结合表观遗传学和转录组学数据，我们鉴定出两个候选基因和，它们可能对调节 SAT 和 VAT 之间不同的代谢和炎症特征至关重要。总之，这些结果揭示了转录调控网络的差异，并丰富了对 SAT 和 VAT 之间不同生物学功能的机制理解。
