Comprehensive analysis of regulation of DNA methyltransferase isoforms in human breast tumors

Significant reprogramming of epigenome is widely described during pathogenesis of breast cancer. Transformation of normal cell to hyperplastic cell and to neoplastic phenotype is associated with aberrant DNA (de)methylation, which, through promoter and enhancer methylation changes, activates oncogenes and silence tumor suppressor genes in variety of tumors including breast. DNA methylation, one of the major epigenetic mechanisms is catalyzed by evolutionarily conserved isoforms namely, DNMT1, DNMT3A and DNMT3B in humans. Over the years, studies have demonstrated intricate and complex regulation of DNMT isoforms at transcriptional, translational and post-translational levels. The recent findings of allosteric regulation of DNMT isoforms and regulation by other interacting chromatin modifying proteins emphasizes functional integrity and their contribution for the development of breast cancer and progression. DNMT isoforms are regulated by several intrinsic and extrinsic parameters. In the present review, we have extensively performed bioinformatics analysis of expression of DNMT isoforms along with their transcriptional and post-transcriptional regulators such as transcription factors, interacting proteins, hormones, cytokines and dietary elements along with their significance during pathogenesis of breast tumors. Our review manuscript provides a comprehensive understanding of key factors regulating DNMT isoforms in breast tumor pathology and documents unsolved issues.