High impact information on RPD3

• Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex [1].
• Biochemical, genetic, and gene-expression analyses show that Rpd3 exists in two distinct complexes [1].
• Rpd3 and Hda1 deacetylate mainly distinct promoters and gene classes where they are recruited largely by novel mechanisms [2].
• We show by co-immunoprecipitation and by the high similarity of their binding maps that Ume1 interacts with Rpd3 [3].
• Finally, we show that comparing the genome-wide pattern of Rpd3 binding with gene expression and histone acetylation in the rpd3 Delta mutant strain reveals new sites of Rpd3 function [3].

Biological context of RPD3

• GCN5-dependent histone H3 acetylation and RPD3-dependent histone H4 deacetylation have distinct, opposing effects on IME2 transcription, during meiosis and during vegetative growth, in budding yeast [4].
• The profiles demonstrate that 40% of endogenous genes located within 20 kb of telomeres are down-regulated by RPD3 deletion [5].
• Finally, bioinformatic analyses indicate that the yeast HDACs RPD3, SIR2, and HDA1 play distinct roles in regulating genes involved in cell cycle progression, amino acid biosynthesis, and carbohydrate transport and utilization, respectively [5].
• Deletion of RPD3 is not lethal but confers phenotypes identical to those caused by spontaneous mutations [6].
• Finally, we find that gcn5 and rpd3 single mutants are not defective in meiosis if acetate is absent and respiration is promoted by a metabolically unrelated carbon source [4].

Anatomical context of RPD3

• Taken together, these data indicate that the transcription factor Swi6p and the Rpd3p-based deacetylase complex act in parallel pathways to activate genes required for cell wall biosynthesis [7].
• We investigated the protein associations and enzymatic requirements for the Xenopus histone deacetylase catalytic subunit RPD3 to direct transcriptional repression in Xenopus oocytes [8].
• Moreover, telomere clustering at the nuclear envelope is perturbed in Deltascp160 cells and disruption of the histone deacetylase RPD3, which is known to improve telomere clustering, rescues telomeric silencing in Deltascp160 cells [9].
• In addition, this fragment encodes Rpd3, a pleiotropic transcription factor (Vidal and Gaber, 1991), and part of Pas8, a protein essential for the biogenesis of peroxisomes (Voorn-Brouwer et al., 1993) [10].
• Developmentally regulated rpd3p homolog specific to the transcriptionally active macronucleus of vegetative Tetrahymena thermophila [11].

Associations of RPD3 with chemical compounds

• Many of these are down-regulated rapidly by TSA, indicating that Rpd3p may also activate transcription [5].
• Rpd3p also appears to activate telomeric genes repressed by the silent information regulator (SIR) proteins directly, possibly by deacetylating lysine 12 of histone H4 [5].
• A sin3 mutant strain lacks detectable levels of phosphatidylethanolamine and elevated levels of phosphatidylcholine (PC) and a rpd3 mutant strain has reduced levels of PC [12].
• Consistent with the role of the Ada proteins in positive regulation of CLN3, deletion of RPD3, encoding a histone deacetylase, prevented the down regulation of CLN3 mRNA in the absence of glucose [13].
• A high molecular weight complex (430,000) is sensitive to HC-toxin and trichostatin A and shows immunoreactivity with an antibody against Cochliobolus HDC2, an enzyme homologous to yeast RPD3 [14].

Physical interactions of RPD3

• The Saccharomyces cerevisiae Sin3 transcriptional repressor is part of a large multiprotein complex that includes the Rpd3 histone deacetylase [15].
• Deletion of RPD3 histone deacetylase causes earlier origin firing and concurrent binding of the replication factor Cdc45p to origins [16].
• We demonstrate that Rpd3 interacts with both Tup1 and Ssn6 [17].
• Hog1 interacts physically with Rpd3 in vivo and in vitro and, on stress, targets the deacetylase to specific osmostress-responsive genes [18].
• Taken together, these data provide evidence that during anaerobiosis, the Rpd3 complex acts at the DAN1 promoter to antagonize the chromatin-mediated repression caused by Mot3 and Rox1 and that chromatin remodeling by Swi/Snf is necessary for normal expression [19].

Regulatory relationships of RPD3

• In this paper we show that full activation of the HO promoter in vivo requires the Gcn5 protein and that defects in this protein can be suppressed by deletion of the RPD3 gene, which encodes a histone deacetylase [20].
• Using a genetic screen, we isolated three TATA-binding protein (TBP) mutants that increase transcription from promoters that are repressed by the Cyc8-Tup1 or Sin3-Rpd3 corepressors or that lack an enhancer element, but not from an equivalently weak promoter with a mutated TATA element [21].
• Ume1p represses meiotic gene transcription in Saccharomyces cerevisiae through interaction with the histone deacetylase Rpd3p [22].
• Role of Histone Deacetylase Rpd3 in Regulating rRNA Gene Transcription and Nucleolar Structure in Yeast [23].

Other interactions of RPD3

• The HDA1 protein (a subunit of the HDA activity) shares sequence similarity to RPD3, a factor required for optimal transcription of certain yeast genes [24].
• These and other results suggest that Gcn5 and Rpd3 play distinct roles, modulating transcription initiation in opposite directions under two different cellular conditions [4].
• We show that the extent of transcriptional regulation of many, apparently unrelated, genes in Saccharomyces cerevisiae is dependent on RPD1 (and RPD3 [M. Vidal and R. F. Gaber, Mol. Cell. Biol. 11:6317-6327, 1991]) [25].
• Furthermore, similar levels of HDAC activity were detected in immunoprecipitates of HA-Pho23, HA-Rpd3, or HA-Sap30 [26].
• The ability of Ume6p, Sin3p and Rpd3p to differentially regulate expression of the phospholipid biosynthetic genes affects phospholipid composition [12].

Analytical, diagnostic and therapeutic context of RPD3

• Deletion of the RPD3 gene extended life span, and there was no additive effect of caloric restriction [27].
• We showed that Myc-Raf60 co-fractionated with Rpd3-TAP by gel filtration chromatography, and both Myc-Rpd3 and Sin3 co-immunoprecipitated with HA-Raf60 [28].
• To elucidate the mechanism underlying RPD3-mediated repression, we screened all promoters in yeast for occupancy by Rpd3p before and after treatment with rapamycin [29].

References