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We are developing new field -- Physical Epigenetics – which we define as deciphering rules of epigenetics with the help of physics and computation. The key premise is that, despite the appearance of daunting complexity, one can still make meaningful structure-function connections in epigenetics based on robust physics-based models. We are looking into establishing these connections at various scales, from the nucleosome to the entire cell nucleus. For example, our models identify unexplored post-translational modifications in the nucleosome core as key to selective control of the accessibility of the genetic material in the nucleosomal DNA. Our most recent collaborative work explores the largely unknown role of nuclear envelope in the structure and, ultimately, function, of chromatin.

Determinants of the 3D architecture of genomes.

3D nuclear architecture is vital to genome function, however its underlying principles are only beginning to emerge. This collaborative project (with I. Sharakhov, entomology) aims to uncover fundamental mechanisms of maintaining and altering nuclear architecture. Solving this problem will significantly improve our understanding of the role of nuclear architecture in regulation of gene expression, DNA double-strand break repair, generation of chromosomal rearrangements, and, ultimately, epigenetic inheritance and disease.

Hierarchy of chromatin compaction in fruit fly (1): from nucleosome arrays (3) to chromatin loops (4) to the whole nucleus at 100 KB resolution (2).
Modeling of giant (polytene) chromosomes in fruit fly