RPD3

RPD3 (Reduced Potassium Dependency 3) is a Class I histone deacetylase (EC 3.5.1.98) that functions as a catalytic subunit in two major chromatin-modifying complexes in S. cerevisiae. The Rpd3L complex, containing regulatory proteins like Ash1 and Ume6, primarily functions in transcriptional repression at specific promoters and in heat stress response. The Rpd3S complex, recruited via Set2-mediated H3K36 methylation, suppresses cryptic transcription within coding regions. RPD3's catalytic activity is essential for both repression and activation of transcription depending on genomic context, cell cycle phase, and stress conditions. Key functions include: (1) negative regulation of transcription by RNA polymerase II at mating-type loci and rDNA; (2) chromatin organization and heterochromatin stabilization; (3) cell cycle regulation via coordination of S-phase genes and G1/S/G2/M transitions; (4) heat stress response; (5) DNA replication timing control via Rpd3L; (6) rDNA silencing and condensation under nutrient stress. RPD3 exhibits context-dependent coactivator activity in heat-responsive and anaerobic gene induction. The protein localizes to the nucleus with dynamic nuclear periphery localization under genotoxic stress.