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

Grant number: 14/10198-5
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): September 15, 2014
Effective date (End): January 14, 2015
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Maria Luiza Silveira Mello
Grantee:Marina Barreto Felisbino
Supervisor: Assam El-Osta
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Research place: Baker IDI Heart & Diabetes Institute, Australia  
Associated to the scholarship:12/03238-5 - Effects of valproic acid and trichostatin A on chromatin organization and its regulation by epigenetic factors in HepG2 cells grown under hyperglycemic conditions, BP.DR


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)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FELISBINO, MARINA BARRETO; ZIEMANN, MARK; KHURANA, ISHANT; OKABE, JUN; AL-HASANI, KEITH; MAXWELL, SCOTT; HARIKRISHNAN, K. N.; MARTINS DE OLIVEIRA, CAMILA BORGES; MELLO, MARIA LUIZA S.; EL-OSTA, ASSAM. Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways. SCIENTIFIC REPORTS, v. 11, n. 1, . (14/10198-5, 10/50015-6, 15/10356-2)

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