Phase-separation in chromatin organization

Abstract

The organization of chromatin into different types of compact versus open states provides a means to fine tune gene regulation. Recent studies have suggested a role for phase-separation in chromatin compaction, raising new possibilities for regulating chromatin compartments. This perspective discusses some specific molecular mechanisms that could leverage such phase-separation processes to control the functions and organization of chromatin.

Figure 1.

(A) The structure of a nucleosome. DNA is in black. Histone H2A is in red, H2B in yellow, H3 in green and H4 in blue. The H3K9me3 mark is schematically shown as a red circle. (B) Domain diagram of an HP1 dimer. HP1 has two structured domains, the CD, which binds the H3K9me3 mark and the CSD, which forms a dimer that serves as binding interface for various protein ligands. HP1 has three intrinsically disordered regions (IDRs), an N-terminal extension (NTE), a hinge (H) and a C-terminal extension (CTE). Interactions made by the NTE and hinge mediate higher-order HP1 oligomerization.

Figure 2.

The schematic shows multiple LLPS droplets across a stretch of the genome and highlights different mechanisms for regulating LLPS in the context of chromatin organization. The droplets are shown in blue and grey. HP1 proteins are shown in green, and other hypothetical chromatin regulators are shown in purple and maroon. Nucleosomes in blue are shown schematically as adopting different shapes to represent different conformations. The H3K9 methyl mark is depicted in red. Thicker arrows represent droplets with higher material strength compared to thinner arrows.