Disease relevance of Rpd3

• In addition, we found that the transcriptional repressor protein, lethal (3) malignant brain tumor protein, L(3)MBT, and the histone deacetylase, Rpd3, associated with the Myb-MuvB complex [1].

Psychiatry related information on Rpd3

• These findings raise the possibility that therapy with HDAC inhibitors may slow or prevent the progressive neurodegeneration seen in Huntington's disease and other polyglutamine-repeat diseases, even after the onset of symptoms [2].

High impact information on Rpd3

• By contrast, the co-repressor proteins Groucho and dCtBP, and the histone deacetylase Rpd3, do not affect establishment but instead maintain repression after the blastoderm stage [3].
• In vivo, HDAC inhibitors arrest ongoing progressive neuronal degeneration induced by polyglutamine repeat expansion, and they reduce lethality in two Drosophila models of polyglutamine disease [2].
• Expression of Httex1p in cultured cells reduces the level of the acetylated histones H3 and H4, and this reduction can be reversed by administering inhibitors of histone deacetylase (HDAC) [2].
• A functional interaction between the histone deacetylase Rpd3 and the corepressor groucho in Drosophila development [4].
• This binding led to recruitment of the histone deacetylase dHDAC1 to the promoter of the gene encoding the antibacterial protein Attacin-A and to local modification of histone acetylation content [5].

Biological context of Rpd3

• Finally, we found that a heterozygous deficiency for the histone deacetylase, Rpd3, masked the radiation-resistant phenotype of both esc and E(Pc) mutants [6].
• PCL and E(Z) colocalize virtually completely on polytene chromosomes and are associated with a subset of RPD3 sites [7].
• We show that RPD3 is required for silencing mediated by a Polycomb response element (PRE) in vivo and that E(Z) and RPD3 are bound to the Ubx PRE in vivo, suggesting that they act directly at the PRE [8].
• We show that Drosophila Hdac1, an Rpd3-type gene, interacts cooperatively with Polycomb group repressors in silencing the homeotic genes that are essential for axial patterning of body segments [9].
• Loss of RPD3 reduces the growth rate of cells but does not cause a distinct cell cycle defect, suggesting that cells are delayed in multiple phases of the cell cycle, including G(2) [10].

Associations of Rpd3 with chemical compounds

• Rpd3 and Hda1 represent two major types of genes encoding trichostatin A-sensitive histone deacetylases [9].
• Transcriptional repression by Gal4-dHDAC1 was blocked by the deacetylase inhibitor, FR901228, and thus, deacetylase activity correlates with repression [11].
• For example, a glycine/proline-rich domain in the central variable region functions to recruit the histone deacetylase Rpd3 to the template [12].
• Flies bearing the aspartic acid eIF-2alpha mutant (HD) transgene displayed a slow growth phenotype and small body size [13].

Physical interactions of Rpd3

• Here we show that the SIN3/RPD3 complex and the corepressor SMRTER are required for Drosophila G(2) phase cell cycle progression [10].
• Consistent with this, recombinant dHDAC1 coimmunoprecipitates with components of the Drosophila NuRD complex and dHDAC3 with an as yet unknown 45-kDa protein [14].
• We suggest a model in which the concerted histone deacetylation and methylation by a SU(VAR)3-9/HDAC1-containing complex leads to a permanent silencing of transcription in particular areas of the genome [15].

Other interactions of Rpd3

• The association of ESC and E(Z) with p55 and RPD3 is conserved in mammals [8].
• Functional interaction between the Drosophila knirps short range transcriptional repressor and RPD3 histone deacetylase [16].
• Two highly conserved histone deacetylases, Sir2 and Rpd3, have been linked to caloric restriction and the extension of longevity [17].
• The relatively mild defects observed in Rpd3 mutants suggest that the recently identified Groucho and dCtBP corepressor proteins do not function solely through the recruitment of histone deacetylases [18].
• Mutation of the histone deacetylase (HDAC) Rpd3 induced genome-wide hyperacetylation, genomic replication and a redistribution of the origin-binding protein ORC2 in amplification-stage cells, independent of effects on transcription [19].

Analytical, diagnostic and therapeutic context of Rpd3

• Longevity regulation by Drosophila Rpd3 deacetylase and caloric restriction [20].
• Cell culture assays demonstrate that Rpd3 potentiates repression by the GP domain [4].
• To get more insight into the biological functions of the individual HDAC family members, we have used RNA interference in combination with microarray analysis in Drosophila S2 cells [21].

References