Chromatin Organization and Phase Separation of Histones

Abstract

A concept that formation of heterochromatin is driven by liquid-liquid phase separation (LLPS) has emerged in recent years. Using live cell fluorescence imaging, we show that the linker histone H1 mediates LLPS of heterochromatin in the human cell nucleus. We also find that the core histone H2A readily undergoes LLPS with DNA and nucleosome arrays of varying length in vitro and in doing so does not disrupt the nucleosome core, as observed by FRET measurements. LLPS with histones is enhanced by the presence of free nucleotides like ATP. Consistently, in cells under ATP depleted conditions, the number of H1 rich liquid-like domains in their nuclei are significantly diminished. These findings add yet another dimension to the role of histones in organizing and maintaining the genome inside the nucleus.