Effect of HDAC inhibitors on the expression of MBD proteins coding genes in breast cancer

Abstract

Methyl-CpG binding domain (MBD) proteins are considered as the decoders of the methyl signature on DNA. This highly conserved family of DNA-binding proteins translates the information represented by methylation patterns into appropriate functional language. MBD proteins bind to the DNA around methylated cytosine bases located particularly in the promoter regions, preventing binding of transcription factors and RNA polymerase and thereby repress transcription. Region-specific DNA hypermethylation is considered as a characteristic hallmark of cancer. MBD proteins are held as the main culprits in perpetuating gene silencing mechanism by interacting with a number of protein partners such as HDACs, hence they are now considered as potential biomarkers for diagnosis and prognosis of malignant transformation. The present study will be conducted to analyse the gene expression status of the methyl-CpG-binding (MBD) proteins - MeCP2, MBD1, MBD2, MBD3 and MBD4 in breast cancer after treatment with HDAC inhibitors TSA and SFN. Study and characterization of the pattern of binding of the MBD proteins will provides a powerful set of epigentic markers for outlining the disruption of critical pathways in tumorigenesis. This study based on MBD protein distribution and occupancy in a gene and tumor type specific context will define a sensitive molecular detection strategy for virtually every human cancer type.