Research Groups > Epigenetics Computational Regulatory Genomics

We study gene regulation at the genome-wide level using methods of computational genomics and epigenomics. The main objects of our research are:

• The structure and function of gene promoters - parts of DNA at the beginning of each gene that contain the information for the docking of molecular machinery that transcribes DNA into RNA;
• The function and genomic distribution of generegulatory elements - parts of DNA at varying distances from promoters that affect the rate/level of transcription;
• The function of transcription factors - proteins that bind to specific motifs in the regulatory elements, and this way affect the rate of the transcription of genes under the controls of those elements;
• Transcription factor proteins are themselves products of gene transcription and translation, and the transcription of genes that encode transcription factors is regulated by other transcription factors and often by that factor itself. The complex regulatory interrelationships of this kind are known as transcriptional regulatory networks (TRNs);
• The association of different modes of regulation with epigenetic marks - chemical modifications of DNA or protein complexes it is packaged with in chromosomes - and their inheritance.

Functional classification of core promoters - Our most recent research has focused on the study of different classes of promoters, which are associated with genes serving different functions. Genes active in all cells and organs have promoters whose DNA composition and the arrangement of functional elements are different from those of genes involved in embryonic development or the genes active only in specific types of mature (terminally differentiated) cells.

Responsiveness of genes to long-range regulation and regulatory territories - Different classes of promoters show different ability to respond to regulatory elements located at larger distances. Developmentally regulated genes are especially responsive to signals from regulatory elements located very far away from them, often placed within or beyond other genes (with different, non-responsive promoters). In other words, genes along the chromosomes are often associated with regulatory territories of vastly different sizes, which are sometimes nested within each other. This often makes it difficult to assign regulatory elements to the correct genes. We are developing methods for making the correct assignments of regulatory elements to the genes they regulate. This is important because many genetic diseases affect distal regulatory elements of developmental genes.

Developmental epigenome - Developmentally regulated genes has a number of other regulatory features that set them apart from other genes. Among the most informative are their epigenetic features - especially specific, reversible chemical modifications of DNA or histones (the proteins that DNA is wrapped around in chromosomes). Our approaches to the study of the role of epigenome in developmental regulation includes the categorisation of genes based on the content and dynamics of the epigenome of their genomic neighbourhood, the development of methods to estimate the span of their regulatory territories, and the study of direct involvement of DNA-binding
regulatory complexes in these territories.