Epigenetic research is indispensable to understand how entire genomes work and integrate environmental information. Epigenetic studies exploit the breakthroughs in GENOMICS by focusing research on the traits and constraints that genomes impose on themselves. There is only one genome per organism; the number of Epigenomes is far grater and equal to the number of cell types in the organism. It is CHROMATIN, the organizing structure of the genome in the nucleus that is unique to each cell type. Chromatin is epigenetically modified in a similar manner the DNA sequence is subjected to mutation. Epigenetic modification affects both the DNA and the protein (both histone and non-histone) component of the eukaryotic chromatin. Histones are epigenetically altered by post translational modifications. It is clear that these modifications play specific regulatory roles in DNA mediated transactions in the nucleus, especially in the regulation of gene expression.

While the mapping of the histone post translational modifications and the identification of their regulatory roles attract much attention today, the central aspect of the Epigenetic studies is the modification of the DNA sequence itself. Genomic sequence is epigenetically modified by cytosine methylation. This modification constitutes a heritable trait that is established early in mammalian development. Importantly, genomic methylation underlies vital developmental phenomena such as genomic imprinting and X-inactivation. Significantly, the deregulation of genomic methylation is implicated in cancer and in several human syndromes. In our lab, we focus research towards the elucidation of the mechanisms that generate and maintain genomic methylation. To uncover genome wide mechanisms that control this process, we use mouse ES cells as an experimental system. ES cells can be differentiated to a number of different cell types and thus, comprise an invaluable tool to address questions relevant to the role of DNA methylation in the regulation of gene expression, cell fate decisions and epigenetic inheritance. To achieve our goals we apply biochemical, molecular, genetic and genomic tools.