Genome-wide analysis of VPA-treated HepG2 cells under hyperglycemic conditions

Abstract

Diabetes is a complex multifactorial disorder characterized by chronic hyperglycemia due to impaired insulin secretion, with numerous pathways influencing its progression. Recent observations suggest that the complexity of the disease cannot be entirely accounted for by genetic predisposition. A compelling argument for an epigenetic component is rapidly emerging. Changes in the epigenetic regulation of gene expression represent potentially important pathogenic mechanisms behind complex diseases. Therapeutic targeting of the enzymes that regulate epigenetic mechanisms such as histone modifications may therefore alleviate some aspects of the disease. The use of histone deacetylase inhibitors (HDACi) in clinical settings is an emerging area of investigation. Recent evidences reveal a role for HDACi in preventing ²-cell inflammatory damage, improving insulin resistance, and positively affecting late diabetic microvascular complications. Although there is a strong rationale for investigate HDACi in diabetes, genome-wide studies associating these situations remain poorly understood. The development of precise genome-wide mapping of chromatin modifications has led to significant advances in our understanding of gene regulatory networks. Therefore, we aim to perform a genome-wide ChIP-seq analysis of a hepatocyte cell line exposed to a hyperglicemic environment and treated with the FDA-approved HDACi valproic acid (VPA). With this approach, we aim at expanding our knowledge about the consequences of HDACi treatment on hyperglycemia. (AU)