PI: Tomáš Stopka Mechanisms Involved in Remodeling of Chromatin Structure during Cell Fate Decisions

Chromatin is a nucleoprotein complex which is engaged in the transfer of biological information via mechanisms identifying DNA code and mechanisms detecting the sequence of posttranslationally modified histone proteins.

This so-called “histone code” determines, among others, the accessibility of chromatin to key molecules that are able to recognize the DNA code: for transcription factors. The accessibility of chromatin structure is accomplished by enzymes belonging to SWI/SNF2 family, which are able to regulate the interaction between DNA and histone proteins and enable a shift or complete revelation of DNA. Identification of protein partners within the SWI/SNF2 family and recognition of key mechanisms of chromatin remodeling – utilizing DNA template in vitro – have enabled to understand fundamental functional properties of chromatin-remodeling proteins.

Main ATPases of the SWI/SNF2 family are mammalian homologs of Brg1 and Smarca5, which play their roles in embryogenesis, cellular specification, replication control, organization of nucleolus, chromosome inactivation, and tumorigenesis.

Project focuses on studying the function that ISWI ATPase designated as Smarca5 (Snf2h, MommeD4, Iswi) in the development of haematopoiesis and in the regulation of leukaemogenesis, pursuant to preliminary results.