Disease relevance of SPT10

• The hypersensitivities of the spt10Delta mutant to the genotoxic agents are rescued by a single copy plasmid carrying the SPT10 gene [1].
• The zinc finger of Spt10p is homologous to that of foamy virus integrase, perhaps suggesting that this integrase is also a sequence-specific DNA-binding protein [2].
• A Cre1 protein fragment from the two zinc fingers to the region similar to the aa-sequence of eucaryotic transcription factors, was expressed in Escherichia coli as a fusion protein with glutathione S-transferase [3].

High impact information on SPT10

• SPT10, a putative acetyltransferase, is required for cell cycle-specific K56 acetylation at histone genes [4].
• Identification of CRE1 as a cytokinin receptor from Arabidopsis [5].
• In the presence of functional RT (from human L1, yeast Tyl or Crithidia CRE1), and in the absence of homologous recombination, an HO endonuclease-induced DSB at the mating type (MAT) locus is the primary site at which a marked cDNA is observed among surviving cells [6].
• GCN5-related histone N-acetyltransferases belong to a diverse superfamily that includes the yeast SPT10 protein [7].
• We found that activity of the plant histidine kinase cytokinin response 1 (Cre1) is also regulated by changes in turgor pressure, in a manner identical to that of Sln1, in the presence of cytokinin [8].

Biological context of SPT10

• Mutations in SPT10 and SPT21 of Saccharomyces cerevisiae have been previously shown to cause two prominent mutant phenotypes: (1) defects in transcription of particular histone genes and (2) suppression of Ty and delta-insertion mutations (Spt(-) phenotype) [9].
• An internal open reading frame triggers nonsense-mediated decay of the yeast SPT10 mRNA [10].
• Targeted acetylation of both H3 and H4 also required the product of the SPT10 gene, which encodes a putative histone acetylase implicated in regulation at core promoters [11].
• We have isolated mutations that fall into two genes, SPT10 and SPT21, that allow the 3' LTRs of Ty1 elements inserted at various positions in the genome of Saccharomyces cerevisiae to act as promoters [12].
• Deletion of the chromatin remodeling gene SPT10 sensitizes yeast cells to a subclass of DNA-damaging agents [1].

Anatomical context of SPT10

• Analyses of chimeric mRNAs used to identify the cis-acting basis for NMD of the SPT10 mRNA indicated that ribosomes scan beyond its initiator AUG and initiate at the next downstream AUG, resulting in premature translation termination [10].

Associations of SPT10 with chemical compounds

• Also, the ability of CCR4 to activate transcription when fused to the LexA DNA binding domain was not specifically enhanced by defects in either SPT10 or SPT6 [13].
• These phenotypes include inositol auxotrophy, impaired telomeric silencing, and synthetic lethality with mutations in SPT10, a gene that encodes a putative histone acetyltransferase [14].
• We reisolated the SPT10 gene in a functional genome-wide screen designed to identify haploid yeast mutants that are hypersensitive to the antitumor drug bleomycin, which acts by damaging DNA [1].
• In contrast, serine mutations in H2A prevent CUP1 shutdown when combined with spt10 deletions [15].
• Certain lysine mutations in H2A alleviate the transcriptional defect in spt10 Delta strains, though CUP1 activation is still delayed in these mutants; however, CUP1 shutdown is normal [15].

Enzymatic interactions of SPT10

• We have investigated whether the corresponding counterpart of filamentous fungi-the Cre1 protein-is also phosphorylated by Snf1 [16].

Regulatory relationships of SPT10

• Histone H2A and Spt10 cooperate to regulate induction and autoregulation of the CUP1 metallothionein [15].
• The SUD1 gene was identified during a hunt for mutants that are able to express an sta1 gene (encoding an extracellular glucoamylase) lacking an upstream activation sequence (UAS) for transcription [17].

Other interactions of SPT10

• Neither the cre1 nor cre2 alleles affected the expression of several other glucose-repressible enzymes [18].
• Both the cre1 and cre2 alleles affected ADHII synthesis irrespective of the allele of the positive effector, ADR1 [18].
• Previous experiments demonstrated that mutations at one histone locus, HTA1-HTB1, do cause lethality when in conjunction with mutations in the SPT10 gene [19].
• In both mutant strains this increase was attributable to stabilization of the SPT10 transcript, an mRNA encoding a transcriptional regulator of HHF2 [10].
• Targeted histone acetylation at the yeast CUP1 promoter requires the transcriptional activator, the TATA boxes, and the putative histone acetylase encoded by SPT10 [11].

Analytical, diagnostic and therapeutic context of SPT10

• Although microarray analysis confirmed that Spt10p is a global regulator, Spt10p was not detected at any of the most strongly affected genes in vivo [20].
• Previous studies have demonstrated that Spt10 and Spt21 are required for the normal transcription of a subset of the histone genes in Saccharomyces cerevisiae, and sequence analysis has suggested that Spt10 is an acetyltransferase [21].
• Chromatin immunoprecipitation experiments indicate that, unlike wild-type Spt10p, the C388S protein does not bind to the promoter of the gene encoding histone H2A (HTA1) in vivo [2].

References