Events and seminars

Chromatin and Epigenome Regulation in a Test Tube

Heritable positioning of the nucleosome and methylated DNA, commonly observed as 5-methylcytosine in CpG dinucleotides, plays a central role in the epigenetic regulation in eukaryotes. The nucleosome, the fundamental genomic DNA folding unit of chromatin, acts as a roadblock for the maintenance of CpG methylation, however. Accordingly, aging- or cancer-associated deterioration of DNA methylation is most pronounced in unaccessible heterochromatin. We study molecular mechanisms that coordinate and support inheritance of these epigenetic signatures in the genome.

Xenopus egg extract is a unique cell-free system, which can recapitulate many chromatin and cell cycle processes. The physiological system is ideal for biochemical dissection of machineries that respond to specific structural and epigenetic features of chromatin. Employing this experimental system, we identified CDCA7 as an evolutionary conserved sensor of hemimethylated CpG and an activator of the nucleosome remodeler HELLS, which assists DNA methylation in heterochromatin. We also characterized the molecular mechanism by which the histone variant H2A.Z, which plays a critical role in gene regulation, is preferentially associated with unmethylated DNA segments. I will talk about these recent findings on the relationship between DNA methylation and the nucleosome, cell cycle-dependent regulation of nucleosome assembly, and our new structural approaches for chromatin biology.