Yeast Rpd3L histone deacetylase couples nutrient shifts to genome-wide chromatin reprogramming

Area of Science:

• Molecular Biology
• Yeast Genetics
• Epigenetics

Background:

• Metabolic flexibility allows yeast to adapt to changing nutrient availability.
• Histone deacetylases (HDACs) play a role in regulating gene expression.
• The function of HDACs at active promoters during metabolic transitions was unclear.

Purpose of the Study:

• To investigate the role of histone deacetylase Rpd3 in metabolic flexibility.
• To understand how Rpd3 mediates chromatin reprogramming during nutrient transitions.
• To resolve the paradox of HDAC enrichment at active promoters.

Main Methods:

• Genome-wide analyses of gene expression and histone acetylation.
• Investigating the localization and function of Rpd3 complexes, particularly Rpd3L.
• Studying yeast mutants lacking Rpd3 or its subunit Pho23.

Main Results:

• Rpd3 mediates nutrient-dependent chromatin reprogramming, coordinating gene shutdown and acetylation balance.
• Rpd3 complexes drive rapid, reversible histone deacetylation at gene promoters and bodies.
• Loss of Rpd3 leads to aberrant gene expression during starvation and impaired respiratory gene activation.

Conclusions:

• HDACs, like Rpd3, act as metabolic gatekeepers, linking nutrient signals to chromatin changes.
• Rpd3 ensures transcriptional fidelity during metabolic transitions in yeast.
• This study clarifies the role of HDACs in regulating gene expression during adaptation.