High impact information on SIN3

• We have found that S. cerevisiae Isw2 complex represses transcription of early meiotic genes during mitotic growth in a parallel pathway to Rpd3-Sin3 histone deacetylase complex [1].
• Here, we show that Sin3 and Rpd3 are specifically required for transcriptional repression by Ume6, a DNA-binding protein that regulates genes involved in meiosis [2].
• We also find that inactivation of the Sin3p/Rpd3p deacetylase complex leads to a high level of acetylation at the HO locus throughout the cell cycle [3].
• Moreover, we describe a SAP30 homolog in yeast that is functionally related to Sin3 and the histone deacetylase Rpd3 [4].
• TIS7 interacts with the mammalian SIN3 histone deacetylase complex in epithelial cells [5].

Biological context of SIN3

• We have cloned the SIN3 gene and determined that a haploid strain with a SIN3 gene disruption is viable [6].
• Mutations in SIN3 and RPD3, which encode components of a histone deacetylase complex, show the same pattern of genetic suppression, and this suppression pattern differs from that seen in a sin4 mutant [7].
• Combinatorial regulation of phospholipid biosynthetic gene expression by the UME6, SIN3 and RPD3 genes [8].
• In addition, sds3 mutants have phenotypes very similar to those seen in sin3 and rpd3 mutants, suggesting that it functions in the same genetic pathway [9].
• A LexA-Sin3 fusion protein represses transcription of promoters with LexA binding sites [10].

Anatomical context of SIN3

• SMRT originally was identified as a corepressor of unliganded retinoic acid and thyroid receptors and forms a repressive complex with a mammalian homolog of the yeast transcriptional repressor SIN3 and the HDAC-1 histone deacetylase [11].

Associations of SIN3 with chemical compounds

• The inferred RPD1 protein contains four regions predicted to take on helix-loop-helix-like secondary structures and three regions (acidic, glutamine rich, and proline rich) reminiscent of the activating domains of transcriptional activators [12].
• A greater reduction in REB1 activity is observed if the sin3 mutant strain is grown in media containing galactose as a carbon source [13].
• 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 [8].
• Complete deletions of RPD3 and the repression adapter SIN3 permitted recombination and early meiotic gene expression when replication was inhibited with hydroxyurea (HU) [14].
• We also show that lysine 16 of histone H4 becomes deacetylated in the proximity of a chromosomal DNA double-strand break in a Sin3p-dependent manner [15].

Physical interactions of SIN3

• The Saccharomyces cerevisiae Sin3 transcriptional repressor is part of a large multiprotein complex that includes the Rpd3 histone deacetylase [10].
• The in vitro levels of the REB1 DNA-binding activity are reduced in extracts prepared from strains bearing a mutation in the SIN3 gene [13].
• Identification of the Sin3-binding site in Ume6 defines a two-step process for conversion of Ume6 from a transcriptional repressor to an activator in yeast [16].
• Mouse homologs of SIN3 have been identified through screens for proteins interacting with the mammalian Mad1 protein, a transcriptional repressor [17].

Regulatory relationships of SIN3

• A Ume6p-binding site was identified in the promoters of genes up-regulated in the sin3 strain [18].
• Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3-Rpd3 histone deacetylase [19].
• Two distinct promoter elements, the upstream repression sequence (URS1) and the INO1 upstream activation sequence (UASINO) both were found to be involved in enabling SIN3 to repress INO1 expression [20].

Other interactions of SIN3

• 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]) [12].
• These results are surprising given that Ume6p, Sin3p and Rpd3p are known to form a complex that represses the expression of a diverse set of yeast genes [21].
• Regulation of INO1 was also observed in the absence of the SIN3 gene product [22].
• The Saccharomyces cerevisiae SIN3 gene, a negative regulator of HO, contains four paired amphipathic helix motifs [6].
• This suggests that SIN3 and SWI1 may play opposite regulatory roles in controlling expression of many yeast genes [23].

Analytical, diagnostic and therapeutic context of SIN3

• Immunofluorescence microscopy with anti-SIN3 antibody demonstrated that SIN3 protein was present in nuclei [6].
• We are unable to demonstrate the direct interaction of SIN3 protein with these activators using the yeast two-hybrid system or co-immunoprecipitation [24].
• We show here that Sin3p is present in a large multiprotein complex with an apparent molecular mass, estimated by gel filtration chromatography, of greater than 2 million Da [25].
• Here we show that growth of a Deltatrk1Deltasin3 double mutant, under K+-limiting conditions or at low pH, is Trk2p-dependent, and by Northern blot analysis we demonstrate that deletion of SIN3 results in transcriptional derepression of TRK2 [26].

References