Epigenetics

Epigenetic refers to the study of heritable changes that occur without a modification in DNA sequence of the genes. It is caused mostly by histone modifications and DNA methylation upon gene expression. Epigenetic defects have been found to be major factors in cancer, genetic disorders as well as in autoimmune diseases and aging.

Cells manage gene expression by wrapping DNA around clusters of globular histone proteins to form nucleosomes. These nucleosomes of DNA and histones are organized into chromatin. Changes to the structure of chromatin influence gene expression. For example, genes are inactivate when the chromatin is condensed, and they are expressed when chromatin is open. These chromatin states are controlled by DNA methylation and histone modifications.

A number of proteins involved in epigenetics interact with histone modifying enzymes like histone methyltransferases (HMTs) and histone deacetylases (HDACs). Disturbing their relationship will almost have severe consequences on the epigenome and chromatin organization. The histone N-terminal sequences are crucial to maintain chromatin stability and they are subject to numerous modifications. Most modifications such as acetylation, methylation and phosphorylation have some role to play in transcriptional regulation and have the potential to be oncogenic if result, for example, to loss of expression of a tumour suppressor gene.

Projects

The Laboratory now has projects related to biochemical and genetic characterization of the enzymes that catalyze arginine methylation.
 
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