Research Activities
Genome organization and epigenetic regulation
1.1. Genomics of non-coding part of genomes:
Non-coding DNA has consistently increased duringevolution of higher eukaryotes. Since the number of genes has remained relatively static during the evolution of complex organisms, it is believed that increased degree of sophisticated regulation of genes has contributed to the increased complexity. Higher proportion of non-coding DNA, including repeats, is likely to provide more complex regulatory potential. We have carried our extensive analysis of simple sequence repeats across species and show that only few among all possible repeats are enriched in complex organisms. We also show that longer stretches of these repeats are more abundant that shorter stretches suggesting positive selection of these elements during evolution of complexity. We propose that repeats play a regulatory role by contributing to the packaging of the genome during cellular differentiation. Repeats, and in particular the simple sequence repeats, are proposed to serve as landmarks that can target regulatory mechanisms to a large number of genomic sites with the help of very few factors and regulate the linked loci in a coordinated manner. Repeats may, therefore, function as common target sites for regulatory mechanisms involved in the packaging and dynamic compartmentalization of the chromatin into active and inactive regions during cellular differentiation.
Researcher(s):
- Dr. Rakesh Mishra & Group
1.2. Bioinformatics of the epigenetic regulatory system:
Polycomb group (PcG) proteins play a key role in epigenetic mechanism that maintains the expression state of a large number of genes. Polycomb (PC) is conserved during evolution and while invertebrates have one PC gene, vertebrates have five or more homologues. It remains unclear if different vertebrate PC homologues have distinct or overlapping functions. We have identified and compared the sequence of ~100 PC homologues in various organisms to analyze similarities and differences that shaped the evolutionary history of this key regulatory protein. This analysis led to the identification of a novel insect specific motif and ten novel and signature motifs in the vertebrate homologue. These finding pave the way to understand the molecular basis of epigenetic mechanisms. Additionally, we identified ‘AT-Hook Like’ in the vertebrate homologues adjacent to the chromodomain, which suggests a three-way ‘PC-histoneH3-DNA’ interaction that can restrict nucleosome dynamics. Our analysis shows that PC is an ancient gene dating back to pre bilaterian origin that has not only been conserved but has also expanded during the evolution of complexity. Unique motifs acquired by each homologue have been maintained for more than 500 millions years indicating their functional relevance in boosting the epigenetic ‘tool kit’.
Researcher(s):
- Dr. Rakesh Mishra & Group