High impact information on UME6

• We describe the genome-wide distribution of the histone deacetylase and repressor Rpd3 and its associated proteins Ume1 and Ume6 in Saccharomyces cerevisiae [1].
• The Isw2 chromatin remodeling complex represses early meiotic genes upon recruitment by Ume6p [2].
• Nuclease digestion analyses revealed that lsw2 complex establishes nuclease-inaccessible chromatin structure near the Ume6p binding site in vivo [2].
• A short region of Ume6 is sufficient to repress transcription, and this repression domain mediates a two-hybrid and physical interaction with Sin3 [3].
• Here we study the mechanism by which RPD3 represses gene activity by examining the acetylation state of histone proteins at UME6-regulated genes [4].

Biological context of UME6

• Role of UME6 in transcriptional regulation of a DNA repair gene in Saccharomyces cerevisiae [5].
• Combinatorial regulation of phospholipid biosynthetic gene expression by the UME6, SIN3 and RPD3 genes [6].
• INO2 expression is regulated by a complex cascade that includes autoregulation, Opi1p-mediated repression and Ume6p-mediated activation [7].
• However, it is unknown how H4 proteins located at genes near UME6-binding sites are affected, nor whether the effect of RPD3 is localized to the promoter regions [4].
• The behavior of insertion and deletion alleles indicates that UME6 is dispensable for mitotic division but is required for meiosis and spore germination [8].

Associations of UME6 with chemical compounds

• Transcriptional repression by UME6 involves deacetylation of lysine 5 of histone H4 by RPD3 [4].
• The UME6 gene encodes a 91-kD protein that contains a C6 zinc cluster motif similar to the DNA-binding domain of GAL4 [8].
• Glucose inhibits Ime1p-Ume6p interaction, and we find that Rim15p accumulation is repressed in glucose-grown cells [9].
• In Saccharomyces cerevisiae, expression of arginine catabolic genes CAR1 and CAR2 in response to exogenous nitrogen availability is mediated by the Ume6 (CargRI)-Sin3 (CargRII)-Rpd3 (CargRIII) complex [10].
• UME6 contains, near the C-terminus, the amino acid sequence-771C-X2-C-X6-C-X6-C-X2-C-X6-C-, in which the spacings of the six Cys residues are identical to those found in 39 N-terminal Cys-rich DNA binding subdomains of fungal transcription factors [11].

Physical interactions of UME6

• 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 [12].
• Yeast Ume6p repressor permits activator binding but restricts TBP binding at the HOP1 promoter [13].

Enzymatic interactions of UME6

• We show here that Rim11p binds to and phosphorylates Ume6p, as well [14].
• These results argue that Ime1p must be phosphorylated to interact with Ume6p [15].

Regulatory relationships of UME6

• A Ume6p-binding site was identified in the promoters of genes up-regulated in the sin3 strain [16].
• Multiple copies of UME6 stimulate expression from UAS(PHR1) and the intact PHR1 gene [5].
• We have shown previously that the UME6 gene positively regulates INO2 expression [17].
• IME1 may activate meiotic genes by modifying a UME6-dependent repression complex at a URS1 site [18].

Other interactions of UME6

• We propose that IME1 modifies UME6 to convert it from a negulator to a positive Regulor [19].
• Thus, UME6 and the URS1 site both have dual negative and positive roles at the IME2 UAS [19].
• 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 [7].
• This suggests that Ume6p does not regulate INO2 expression indirectly by regulating OPI1 expression [7].
• We also show that the UME6 gene does not affect the expression of an OPI1-cat reporter [7].
• During mitotic cell division, Ume6p is protected from destruction by protein kinase A phosphorylation of Cdc20p [20].

Analytical, diagnostic and therapeutic context of UME6

• Here, through sequence analysis, we demonstrate that UME6 and CAR80 are identical [8].
• Here we find that Mck1p-Ume6p interaction is detectable by two-hybrid assays and that meiosis in a partially defective rim11-K68R mutant is completely dependent on Mck1p [21].
• While URS1 is bound in vitro by the Buf and Ume6 repressor proteins, we demonstrate for the first time by electrophoretic mobility shift assays and interference footprinting that the UASH site interacts in vitro with a novel factor called UBF (UASH binding factor) which is present in haploid and diploid cycling, as well as sporulating cells [22].

References