Rpd3S

Rpd3S is a transcription-coupled histone deacetylase complex in the budding yeast Saccharomyces cerevisiae. It forms from the Rpd3 family of histone deacetylases and is distinguished from the Rpd3L complex by its subunit composition and genomic distribution: Rpd3S associates with transcribed regions within gene bodies, whereas Rpd3L concentrates at promoters.

Core components of Rpd3S include the catalytic histone deacetylase Rpd3 and the scaffold protein Sin3. The complex is defined by the presence of two additional subunits, Eaf3 and Rco1, which read the histone H3 lysine 36 methylation marks laid down by Set2 during transcription. Eaf3 contains a chromodomain, and Rco1 contributes a reader module that helps target the complex to methylated coding regions.

Functionally, Rpd3S is recruited to coding regions by H3K36 methylation during transcription and deacetylates histone tails in those regions. This activity counteracts histone acetylation waves associated with transcription, helping to maintain chromatin compaction and prevent cryptic transcription initiation within gene bodies. Genetic disruption of Rpd3S components leads to increased cryptic transcription and altered gene expression patterns.

Rpd3S provides a model for how histone deacetylation is coupled to transcriptional elongation and chromatin state in yeast. Its conserved features have informed studies of related HDAC complexes in other organisms, where analogous mechanisms link histone methylation, reader proteins, and deacetylation to transcriptional fidelity.