Epi-nucleosome’ technologies (Precise reconstitution of epigenetic nucleosomes)
Epigenetic information is ‘added’ onto genetic information, which regulates gene expression of individual cell.This ‘additional’ information is substantialized by chemical modification onto nucleosome that is composed of DNA and histone proteins. The modification of the histone proteins is recorded on the nucleosome, as combinations of the kind of modifications (acetylation, methylation, phosphorylation etc.), and the kind of the subunit and residues modified. These combinatorial information is maintained, recognized and converted in the cell. Although the regulatory mechanisms of epigenetics have been extensively analyzed at the cellular level, biochemical analyses mostly remained at those using modified peptides as pseudo-substrate of chromatin.
Epigenetics Drug Discovery Unit has been developing the technologies to precisely reconstitute the nucleosome with designed epigenetic information (‘epi-nucleosome’), through the understanding of translation mechanisms and applied biochemistry. Regarding the histone acetylation, in particular, we have established in vitro reconstitution of epi-nucleosome containing multiple and site-specific lysine acetylation that is a hallmark of transcriptional activation. Our technologies will be useful for understanding of the molecular mechanisms of human gene expression, and direct screening and evaluation of biomolecules targeting the gene expression regulatory mechanisms.