Chromatin condensation fluctuations rather than steady-state predict chromatin accessibility

Area of Science:

• Molecular Biology
• Cell Biology
• Biophysics

Background:

• Chromatin accessibility is vital for genome functions, but the dynamics of higher-order structures remain unclear.
• Understanding chromatin dynamics is key to deciphering gene regulation and cellular processes.

Purpose of the Study:

• To investigate the dynamic properties of chromatin condensation and its impact on protein accessibility in live cells.
• To explore the mechanisms regulating chromatin condensation fluctuations and their relationship with histone acetylation.

Main Methods:

• Utilized the microenvironment-sensitive fluorescence lifetime of EGFP-H4 histone to map chromatin dynamics in live cell nuclei.
• Assessed the interaction between chromatin and a specific acetylation recognition domain (TAFII250's double bromodomain, dBD).

Main Results:

• Identified spontaneous chromatin condensation fluctuations distinct from stable condensation.
• Demonstrated that fluctuation amplitudes are influenced by sub-nuclear localization, histone acetylation, and ATP.
• Revealed that histone H4 accessibility to dBD is predicted by condensation fluctuations, not condensation levels or acetylation alone.

Conclusions:

• Chromatin condensation fluctuations are a critical determinant of protein factor accessibility.
• Histone acetylation and ATP-dependent mechanisms modulate these fluctuations, impacting genome accessibility.
• This study provides a novel perspective on chromatin dynamics and its role in regulating genome accessibility.