Psychiatry related information on SPT2

• Administration of NOS inhibitors and NO scavenger Hb increased the pain threshold capacity significantly, whereas NO donors SIN-1, SNP and NO precursor L-arginine were found to be hyperalgesic [1].

High impact information on SPT2

• Deletion of the SIN1 gene, which codes for a DNA-binding protein that negatively regulates HO transcription, restores INO1 transcription and reduces the cold sensitivity of such strains [2].
• Recruitment of mRNA cleavage/polyadenylation machinery by the yeast chromatin protein Sin1p/Spt2p [3].
• This conclusion is based on the following findings: Sin1p/Spt2 frequently binds specifically downstream of many ORFs but almost always upstream of the first polyadenylation site [3].
• Furthermore, using recombinant molecules in vitro, we show that the N terminal of SIN1 is sufficient to bind a portion of CDC23 consisting solely of tetratrico peptide repeats [4].
• In an effort to understand the basis for these phenotypes, we employed the yeast two-hybrid system to identify proteins that interact with SIN1 in vivo [4].

Biological context of SPT2

• We show here that several alleles carrying C-terminal deletions as well as point mutations in the C-terminal domain of the SPT2 protein exhibit a dominant suppressor phenotype [5].
• We have cloned SIN1 and found that it is identical to the previously identified gene SPT2, mutations in which allow transcription from certain mutated regulatory regions [6].
• Because sin1 mutants exhibit increased loss of chromosome III, SIN1 may also play a role in fidelity of chromosome segregation [6].
• To assess the significance of this structural similarity and identify domains of SPT2 functionally important in the regulation of his4-912 delta, we have studied recessive and dominant spt2 mutations created by in vitro mutagenesis [5].
• When the DNA sequence to which the protein complex binds is placed in a CYC1 promoter lacking a UAS (upstream activating sequence), it can serve as a weak UAS in a SIN1 dependent way [7].

Anatomical context of SPT2

• NO evolving from the spontaneous decomposition of 3-morpholinosydnonimine (SIN-1) was trapped by Fe(2+)-diethyldithiocarbamate (DETC) complex dissolved in yeast cell membranes [8].

Associations of SPT2 with chemical compounds

• We show that SIN1 is concentrated in the nucleus and binds to DNA with little or no sequence specificity in vitro [6].
• We found that three domains of Sin1p/Spt2p fused to glutathione S-transferase can each bind independently in a structure-specific manner to 4WJDNA as measured in a gel mobility shift assay [9].
• NO generated by NO synthase and by SIN-1 accumulated at a constant rate for 1 h, as measured by continuous e.p.r. registration at 37 degrees C. The formation of e.p.r.-detectable NO by NO synthases was inhibited by NG-nitro-L-arginine [10].
• Slow, continuous production of peroxynitrite from decomposition of SIN-1 inactivated alcohol dehydrogenase as effectively as bolus addition [11].
• In addition, Ss-12 and yeast cells were more susceptible than Ss-7 to the direct fungicidal activity of the NO donors S-nitroso-N-acetyl-DL-penicillamine (SNAP), S-nitrosoglutathione (GSNO) and 3-morpholinosydnonimine (SIN-1) [12].

Physical interactions of SPT2

• SIN1 interacts with a protein that binds the URS1 region of the yeast HO gene [7].
• Furthermore, we show, using recombinant molecules in vitro, that a short 27 amino acid sequence near the N-terminal of SIN1 is sufficient to bind SAP1 [13].

Regulatory relationships of SPT2

• The ability of spt2 mutations to suppress the transcriptional interference caused by the delta promoter insertion his-4-912 delta correlates with an increase in wild-type HIS4 mRNA levels [5].
• Characterization of a short unique sequence in the yeast HO gene promoter that regulates HO transcription in a SIN1 dependent manner [14].

Other interactions of SPT2

• Addition of random DNA segments to a test promoter alters regulation by SIN1 in a manner similar to addition of a segment from the HO upstream region [6].
• The Saccharomyces cerevisiae SPT2 gene was identified by genetic screens for mutations which are suppressors of Ty and delta insertional mutations at the HIS4 locus [5].
• The predicted SIN1/SPT2 protein has a distinctive amino acid composition (45% charged residues, 25% basic and 20% acidic) and has similarity to the mammalian HMG1 protein, a nonhistone component of chromatin [6].
• We therefore attempted to walk to RAD4 from the neighboring SPT2 gene and obtained an integrating derivative of a plasmid isolated by Roeder et al [15].
• Association of yeast SAP1, a novel member of the 'AAA' ATPase family of proteins, with the chromatin protein SIN1 [13].

Analytical, diagnostic and therapeutic context of SPT2

• In addition, genome-wide and gene-specific chromatin immunoprecipitation analyses suggest that Spt2 is primarily associated with coding regions in a transcription-dependent fashion [16].
• Sequence alignment of Sin1p/Spt2p homologues from 11 different yeast species showed conservation of several domains [9].
• Reliability and sensitivity of the SPT1- and SPT2-based biosensors were good, but varied with the wastewater [17].

References