Regulatory circuit of p300 and DNA Methylation in cancer

Abstract

p300 is a Histone acetyltransferase which mainly acts as a global transcriptional coactivator and plays important roles in various biological processes including cell proliferation, differentiation, and apoptosis. DNMTs faithfully replicate the existing methylation marks and propagate the methylation pattern across successive cell generations. Since p300 is an acetyltransferase it activates many genes to express, thus encouraging transcriptional activity whereas DNA methylation represses the expression of the genome leading to silencing of genes. Therefore, a homeostatic balance between the two transcriptional states is maintained by a co-ordinated and concerted interplay between these two opposing epigenomic manipulations. Hence, the aberrant activity of both p300 and DNMTs may be cause malignant transformation leading to cancer. The present study was carried out to investigate the relationship between p300 and DNMTs so as to find a correlation between their expression and activity in cancer tissues. The mechanisms by which the inactivation of p300 contributes to carcinogenesis have not been fully revealed. Normally, the expression of p300 should remain at base levels in normal tissues. In cancer cells its expression is likely to be higher since it is a transcriptional coactivator. The results that are obtained might be because of the activation of the promoter regions of p300 by some other epigenetic mechanisms such as DNA methylation. Further studies in this area might provide an in-depth knowledge regarding the above two phenomena and provide ideas about novel networking between the various epigenetic modifications.