Expression noise and acetylation profiles distinguish HDAC functions

Area of Science:

• Molecular Biology
• Epigenetics
• Systems Biology

Background:

• Gene expression exhibits significant cell-to-cell variation, known as noise.
• This noise is influenced by the chromatin environment and gene expression regulatory processes.

Purpose of the Study:

• To identify chromatin factors that modulate gene expression noise in S. cerevisiae.
• To elucidate the regulatory mechanisms underlying noise modulation using a theoretical model.

Main Methods:

• Screening of chromatin factors affecting gene expression noise in S. cerevisiae.
• Analysis using a theoretical model correlating noise with mean expression.
• Mapping of H3K9ac upon deletion of histone deacetylase complex subunits and ubH2B effectors.

Main Results:

• Distinct roles for Rpd3(L) and Set3 histone deacetylase complexes in regulating gene expression noise were predicted.
• Both complexes repressed gene expression, but Rpd3(L)C reduced transcriptional burst frequency, while Set3C reduced burst size.
• H2B monoubiquitination (ubH2B) also decreased burst size.
• ubH2B and Set3C function in a common pathway affecting PolII processivity, whereas Rpd3(L)C acts earlier in the regulatory pathway.

Conclusions:

• Chromatin factors, specifically histone deacetylase complexes and H2B monoubiquitination, play distinct roles in controlling gene expression noise.
• Rpd3(L)C and Set3C differentially regulate transcriptional burst dynamics, impacting gene expression levels and variability.
• Understanding these mechanisms provides insights into the regulation of gene expression and cellular heterogeneity.