TY - JOUR

T1 - Biology and Physics of Heterochromatin-Like Domains/Complexes

AU - Singh, Prim B.

AU - Belyakin, Stepan N.

AU - Laktionov, Petr P.

PY - 2020/8/11

Y1 - 2020/8/11

N2 - The hallmarks of constitutive heterochromatin, HP1 and H3K9me2/3, assemble heterochromatin-like domains/complexes outside canonical constitutively heterochromatic territories where they regulate chromatin template-dependent processes. Domains are more than 100 kb in size; complexes less than 100 kb. They are present in the genomes of organisms ranging from fission yeast to human, with an expansion in size and number in mammals. Some of the likely functions of domains/complexes include silencing of the donor mating type region in fission yeast, preservation of DNA methylation at imprinted germline differentially methylated regions (gDMRs) and regulation of the phylotypic progression during vertebrate development. Far cis- and trans-contacts between micro-phase separated domains/complexes in mammalian nuclei contribute to the emergence of epigenetic compartmental domains (ECDs) detected in Hi-C maps. A thermodynamic description of micro-phase separation of heterochromatin-like domains/complexes may require a gestalt shift away from the monomer as the "unit of incompatibility" that determines the sign and magnitude of the Flory-Huggins parameter, χ. Instead, a more dynamic structure, the oligo-nucleosomal "clutch", consisting of between 2 and 10 nucleosomes is both the long sought-after secondary structure of chromatin and its unit of incompatibility. Based on this assumption we present a simple theoretical framework that enables an estimation of χ for domains/complexes flanked by euchromatin and thereby an indication of their tendency to phase separate. The degree of phase separation is specified by χN, where N is the number of "clutches" in a domain/complex. Our approach could provide an additional tool for understanding the biophysics of the 3D genome.

AB - The hallmarks of constitutive heterochromatin, HP1 and H3K9me2/3, assemble heterochromatin-like domains/complexes outside canonical constitutively heterochromatic territories where they regulate chromatin template-dependent processes. Domains are more than 100 kb in size; complexes less than 100 kb. They are present in the genomes of organisms ranging from fission yeast to human, with an expansion in size and number in mammals. Some of the likely functions of domains/complexes include silencing of the donor mating type region in fission yeast, preservation of DNA methylation at imprinted germline differentially methylated regions (gDMRs) and regulation of the phylotypic progression during vertebrate development. Far cis- and trans-contacts between micro-phase separated domains/complexes in mammalian nuclei contribute to the emergence of epigenetic compartmental domains (ECDs) detected in Hi-C maps. A thermodynamic description of micro-phase separation of heterochromatin-like domains/complexes may require a gestalt shift away from the monomer as the "unit of incompatibility" that determines the sign and magnitude of the Flory-Huggins parameter, χ. Instead, a more dynamic structure, the oligo-nucleosomal "clutch", consisting of between 2 and 10 nucleosomes is both the long sought-after secondary structure of chromatin and its unit of incompatibility. Based on this assumption we present a simple theoretical framework that enables an estimation of χ for domains/complexes flanked by euchromatin and thereby an indication of their tendency to phase separate. The degree of phase separation is specified by χN, where N is the number of "clutches" in a domain/complex. Our approach could provide an additional tool for understanding the biophysics of the 3D genome.

KW - block copolymers

KW - epigenetic compartmental domains

KW - Flory–Huggins parameter χ

KW - H3K9me2/3

KW - HP1

KW - unit of incompatibility

KW - CRYOELECTRON MICROSCOPY

KW - ZINC-FINGER PROTEINS

KW - Flory-Huggins parameter chi

KW - DROSOPHILA HETEROCHROMATIN

KW - HOX GENES

KW - DNA METHYLATION DYNAMICS

KW - POSITION-EFFECT VARIEGATION

KW - HISTONE H3

KW - STRUCTURAL BASIS

KW - EMBRYONIC STEM-CELLS

KW - CHROME SHADOW DOMAIN

UR - http://www.scopus.com/inward/record.url?scp=85089487951&partnerID=8YFLogxK

U2 - 10.3390/cells9081881

DO - 10.3390/cells9081881

M3 - Review article

C2 - 32796726

AN - SCOPUS:85089487951

VL - 9

JO - Cells

JF - Cells

SN - 2073-4409

IS - 8

M1 - 1881

ER -