HP1 protein as a key regulator of microphase separation of heterochromatin

Proteins of the HP1 family (Heterochromatin Protein 1) play a key role in the organization of the three-dimensional structure of the genome, participating in the stabilization of heterochromatin and the formation of spatial compartments of the nucleus. For a long time, it was believed that HP1 realizes its functions through the mechanisms of liquid-phase separation (LLPS), but recent data indicate a more relevant role of microphase separation leading to the formation of heterochromatin nanodomains.

The review presents current concepts of the mechanisms of chromatin compartmentalization with the participation of HP1, including its binding to H3K9me2/3-modified nucleosomes , the ability to dimerize and form stable internucleosomal interactions. Particular attention is paid to heterochromatin nanodomains as structural units of microphase separation, their initiation by ATRX, PAX3/9 and ADNP proteins, as well as the thermodynamic parameters regulating their size and stability. The differences between the microphase separation and collapsed globule models , the role of HP1 in embryonic development and cell differentiation, and the involvement of histone H1 and other factors in the maintenance of B-compartments are discussed. The presented data highlight the importance of HP1 in shaping the nuclear epigenetic landscape and open up prospects for further biophysical and biomedical research in the field of regulation of genomic architecture.

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