Enhancer regions show high histone H3.3 turnover that changes during differentiation

Area of Science:

• Epigenetics and Chromatin Biology
• Developmental Biology
• Genomics

Background:

• DNA organization into chromatin is dynamic, with nucleosome displacement crucial for protein access to DNA.
• Understanding nucleosome dynamics during cell differentiation is key to deciphering gene regulation.

Purpose of the Study:

• To quantitatively assess histone H3.3 turnover genome-wide during mouse embryonic stem cell (ESC) differentiation.
• To identify gene regulatory regions based on nucleosome dynamics without prior assumptions.
• To investigate changes in histone turnover during differentiation.

Main Methods:

• Utilized a technique called time-ChIP (chromatin immunoprecipitation) to measure histone H3.3 turnover.
• Performed genome-wide assessment of histone turnover during mouse ESC differentiation.
• Correlated histone turnover with DNA accessibility and Polycomb-Group occupancy.

Main Results:

• High histone H3.3 turnover identified gene regulatory regions, including enhancers and super-enhancers.
• Repressive Polycomb-Group regions exhibited low turnover in ESCs.
• Histone turnover correlated positively with DNA accessibility and showed significant changes at enhancers upon differentiation.

Conclusions:

• Time-ChIP measurement of histone turnover effectively identifies active regulatory elements.
• Active enhancers are highly dynamic in ESCs.
• Changes in dynamic nucleosomes during differentiation predominantly occur at enhancers.