Epigenetics in Development and Cancer

Abstract

Epigenetics is the study of mitotically and/or meiotically heritable changes in gene function without changes in the underlying DNA sequence, thus representating a critical mechanism that allows a remarkably stable propagation of gene activity states over many cell generations. The major epigenetic signals include DNA methylation/demethylation, post-translational reversible covalent modifications of the histone proteins (for examples: acetylation, methylation, phosphorylation, ubiquitination etc.), histone replacements by histone variants and gene regulation by non-coding RNAs. These modifications influence the transcriptional state and regulate the genome for proper cell-cycle progression, differentiation and development and also play an important role in stem cell renewal. Epigenetics is emerging as epigenetic inheritance is essential for development as well as important for critical cellular processes such as gene transcription, differentiation, and protection against viral genomes. During mammalian development, just after fertilization paternal genome undergoes drastic demethylation whereas maternal genome remains intact. Later on pattern of methylation of DNA is established in subsequent stages of development. On the other hand, emerging evidences on aberrant epigenetic states may be linked with various disease phenotypes and malignant transformation. Epigenetic and genetic mechanisms work in tandem to silence the transcription of key cellular genes and destabilize the genome, leading to a host of pathological conditions and tumor development. Investigations in my laboratory are progressing on fundamental mechanisms of reversible methylation modifications of DNA during development and regulation of transcription, reversible acetylation and methylation modifications of Histone 3, mainly, at Lysine 4 and 9 residues (H3K4 and H3K9), co-relation between chromatin dynamics and epigenetic modifications, microRNA mediated gene silencing and correlation with the other epigenetic modulators. Role of bioactive molecules in modulation of epigenetic marks, and computational approach to epigenomics study; leading to “Epigenoformatics”.