Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity

نویسندگان

  • Maria Keller
  • Lydia Hopp
  • Xuanshi Liu
  • Tobias Wohland
  • Kerstin Rohde
  • Raffaella Cancello
  • Matthias Klös
  • Karl Bacos
  • Matthias Kern
  • Fabian Eichelmann
  • Arne Dietrich
  • Michael R. Schön
  • Daniel Gärtner
  • Tobias Lohmann
  • Miriam Dreßler
  • Michael Stumvoll
  • Peter Kovacs
  • Anna-Maria DiBlasio
  • Charlotte Ling
  • Hans Binder
  • Matthias Blüher
  • Yvonne Böttcher
چکیده

OBJECTIVE/METHODS DNA methylation plays an important role in obesity and related metabolic complications. We examined genome-wide DNA promoter methylation along with mRNA profiles in paired samples of human subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from non-obese vs. obese individuals. RESULTS We identified negatively correlated methylation and expression of several obesity-associated genes in our discovery dataset and in silico replicated ETV6 in two independent cohorts. Further, we identified six adipose tissue depot-specific genes (HAND2, HOXC6, PPARG, SORBS2, CD36, and CLDN1). The effects were further supported in additional independent cohorts. Our top hits might play a role in adipogenesis and differentiation, obesity, lipid metabolism, and adipose tissue expandability. Finally, we show that in vitro methylation of SORBS2 directly represses gene expression. CONCLUSIONS Taken together, our data show distinct tissue specific epigenetic alterations which associate with obesity.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

A Six Months Exercise Intervention Influences the Genome-wide DNA Methylation Pattern in Human Adipose Tissue

Epigenetic mechanisms are implicated in gene regulation and the development of different diseases. The epigenome differs between cell types and has until now only been characterized for a few human tissues. Environmental factors potentially alter the epigenome. Here we describe the genome-wide pattern of DNA methylation in human adipose tissue from 23 healthy men, with a previous low level of p...

متن کامل

Predicting CpG Islands and DNA Methlation in the Cow Genome Using DNA Microarray Meta-Analysis and Genome Wide Scanning

DNA methylation is a type of epigenetic changes that directly affects DNA. In mammals, DNA methylation is essential for fetal development and stem cell differentiation and this phenomenon essentially occurs within the CpG islands. In this study, two methods were used to study the DNA methylation profile of cow genome. In the first method, the DNA methylation profile of the differentially expres...

متن کامل

A Genome-Wide mQTL Analysis in Human Adipose Tissue Identifies Genetic Variants Associated with DNA Methylation, Gene Expression and Metabolic Traits

Little is known about the extent to which interactions between genetics and epigenetics may affect the risk of complex metabolic diseases and/or their intermediary phenotypes. We performed a genome-wide DNA methylation quantitative trait locus (mQTL) analysis in human adipose tissue of 119 men, where 592,794 single nucleotide polymorphisms (SNPs) were related to DNA methylation of 477,891 CpG s...

متن کامل

A Stratified Transcriptomics Analysis of Polygenic Fat and Lean Mouse Adipose Tissues Identifies Novel Candidate Obesity Genes

BACKGROUND Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach w...

متن کامل

Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood.

Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed the DNA methylation of ∼480 000 sites in human adipose tissue from 96 males and 94 females and related methylation to age, BMI and HbA1c. We also compared epigenetic signat...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2017