RNA polymerase II coordinates histone deacetylation at active promoters

Area of Science:

• Molecular Biology
• Epigenetics
• Gene Regulation

Background:

• Nucleosomes with specific histone modifications and variants mark active gene promoters.
• These marks are believed to create an open chromatin structure conducive to transcription.
• Conflicting evidence exists regarding the dependence of these histone modifications on active transcription.

Purpose of the Study:

• To investigate the relationship between active histone modifications and transcription initiation.
• To determine if active histone modifications require ongoing transcription.

Main Methods:

• Inhibition of transcription initiation using triptolide to degrade RNA polymerase II.
• Analysis of histone modifications at transcription start sites (TSSs) and enhancers.
• Assessment of p300 activity and histone deacetylase inhibition.

Main Results:

• Active histone modifications at TSSs and enhancers were independent of transcription initiation.
• Blocking transcription initiation led to increased histone acetylation and H2AZ incorporation at active TSSs.
• This increase was independent of p300 activity but was masked by histone deacetylase inhibition.

Conclusions:

• Active histone modifications are established independently of transcription.
• Transcription likely plays a role in removing these modifications to regulate gene expression.
• This suggests a feedback mechanism where transcription limits its own initiation through modification removal.