Chromatin accessibility landscape of stromal subpopulations reveals distinct metabolic and inflammatory features of porcine subcutaneous and visceral adipose tissue.
Chromatin accessibility landscape of stromal subpopulations reveals distinct metabolic and inflammatory features of porcine subcutaneous and visceral adipose tissue.
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基质亚群的染色质可及性景观揭示了猪皮下和内脏脂肪组织的独特代谢和炎症特征
作者：
Sun, Wenyang;Zhang, Tinghuan;Hu, Silu;Tang, Qianzi;Long, Xi;Yang, Xu;Gun, Shuangbao;Chen, Lei
关键词：
背景内脏脂肪组织（VAT）中的脂肪蓄积增加了肥胖代谢紊乱的风险，而皮下脂肪组织（SAT）的蓄积与较低的风险相关，并且可能具有保护作用。以前的研究揭示了SAT和VAT之间的基因表达谱差异;然而，染色质可及性景观差异以及顺式调控元件如何控制SAT和VAT之间的基因表达变化尚不清楚。方法以猪为实验动物，采用DNA酶测序法（DNase-seq）分析两种脂肪基质血管组分（SVFs）染色质可及性的差异。使用来自DNase-seq、H3 K27 ac ChIP-测序（ChIP-seq）和RNA-测序（RNA-seq）的综合数据，我们研究了调控位点复杂性如何调控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库的不同生物学功能产生的影响。结果SAT和VAT的SVF（S-SVF和V-SVF）具有不同的染色质可及性景观。差异DNA酶I超敏位点（DHS）相关基因，这表明动态染色质可及性，主要参与代谢过程和炎症反应。此外，Krüppel样转录因子家族在差异DHS中富集。此外，染色质可及性数据与差异基因表达高度相关，如使用H3 K27 ac ChIP-seq和RNA-seq数据所示，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，我们确定了两个候选基因，NR 1D 1和NRM，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之间不同生物功能的机械理解。
Background 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. Methods 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. Results 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, NR1D1 and CRYM, 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.
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影响因子：
16
作者：
Calo, Eliezer;Wysocka, Joanna
通讯作者：
Wysocka, Joanna
DOI：
10.1038/nrm3949
发表时间：
2015-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Heinz S;Romanoski CE;Benner C;Glass CK
通讯作者：
Glass CK
影响因子：
7.5
作者：
Bora P;Majumdar AS
通讯作者：
Majumdar AS
影响因子：
7.7
作者：
Bell-Anderson KS;Funnell AP;Williams H;Mat Jusoh H;Scully T;Lim WF;Burdach JG;Mak KS;Knights AJ;Hoy AJ;Nicholas HR;Sainsbury A;Turner N;Pearson RC;Crossley M
通讯作者：
Crossley M
影响因子：
4.8
作者：
Li, D;Yea, S;Walsh, MJ
通讯作者：
Walsh, MJ