GSE173277
ATAC-seq and multi-omics analysis of human liver highlight a hepatocyte-specific enhancer for ACOT1 regulating the balance of acyl-CoA and free fatty acids in type 2 diabetes.
ATAC-seq (assay for transposase-accessible chromatin followed by sequencing) is widely used to decode chromatin accessibility. Here we performed high-sensitive ATAC-seq in 9 human liver samples from normal and T2D donors, and identified a set of differentially accessible regions (DARs). DARs were overlapped with publicly available CREs databases and integrated with multi-omics data to identify candidates for further experimental validations. We identified 7 DARs that mark putative regulatory elements including a candidate enhancer for the ACOT1 gene that regulates the balance of acyl-CoA and free fatty acids in the cytoplasm. The relevance of ACOT1 regulation in T2D was supported by the analysis of transcriptomics and proteomics data in liver tissue.  Conclusions: Our strategy that integrates chromatin accessibility with DNA binding and other types of omics provides novel insights towards the role of genetic regulation in complex multifactorial diseases such as T2D. Overall design: ATAC-seq perfomed on 11 liver samples, 3 samples (L9, L10 and L11) were harvested from donor diagnosed with T2D, 8 from control donors characterized by normoglycemia, and each sample has two replicates