The solid and liquid states of chromatin

Area of Science:

• Molecular Biology
• Biophysics
• Genomics

Background:

• Phase separation is a fundamental biophysical process.
• Chromatin, the complex of DNA and proteins, plays a crucial role in genome organization.
• Understanding chromatin's physical state is key to deciphering its functions.

Purpose of the Study:

• To review the principles of phase separation in biological systems.
• To comprehensively discuss chromatin phase separation, including its history and mechanisms.
• To explore the liquid and solid states of chromatin within the nucleus.

Main Methods:

• Literature review of chromatin aggregation studies over 60 years.
• Analysis of evidence for liquid-solid phase separation (LSPS) and liquid-liquid phase separation (LLPS) in chromatin.
• Evaluation of chromatin-associated proteins' phase separation behavior in vitro and in vivo.

Main Results:

• Chromatin aggregation is a physiologically relevant liquid-solid phase separation (LSPS) process driven by self-interaction.
• Under specific conditions, chromatin can exhibit liquid-liquid phase separation (LLPS).
• Chromatin-associated proteins can undergo LLPS, with some requiring DNA or nucleosomes.

Conclusions:

• Chromatin exhibits a dual nature, behaving as a solid on the mesoscale and exhibiting mobile nucleosomes on the nanoscale.
• This viscoelasticity, driven by chromatin self-interaction, is critical for genome structure.
• Chromatin phase separation is a key mechanism for nuclear organization and function.