Disease relevance of e(y)1

• The latter is the main cause of dramatic underdevelopment of the ovaries and sterility of females bearing the e(y)1 mutation [1].

High impact information on e(y)1

• Like histones H3 and H4, dTAFII42 and dTAFII62 form an intimate heterodimer by extensive hydrophobic contacts between the paired molecules [2].
• Mutagenesis studies in combination with protein binding experiments and reconstituted transcription reactions identified two independent activation domains of BCD that target different coactivator subunits (TAFII110 and TAFII60) of the basal transcription factor IID (TFIID) [3].
• Within the basal transcription factor complex TFIID, two specific targets, TAFII110 and TAFII60, served as coactivators to mediate transcriptional activation by these two enhancer binding proteins [4].
• Regulation of transcription initiation by RNA polymerase II requires TFIID, a multisubunit complex composed of the TATA binding protein (TBP) and at least seven tightly associated factors (TAFs) [5].
• These results suggest that TAFIIs contribute to the activation of transcription in vivo and support the hypothesis that subunits of TFIID may serve as targets of enhancer binding proteins [6].

Biological context of e(y)1

• Weak hypomorph mutations in the enhancer of yellow genes, e(y)1 and e(y)2, of Drosophila melanogaster were discovered during the search for genes involved in the organization of interaction between enhancers and promoters [7].
• p53 transcriptional activation mediated by coactivators TAFII40 and TAFII60 [8].
• A double point mutation in the activation domain of p53 impaired the ability of this domain to activate transcription and, simultaneously, its ability to interact with both TAFII40 and TAFII60 [8].
• The close proximity of the VP16 and TAF40 binding sites on the surface of TFIIB suggests that this region could act as a regulatory interface mediating the effects of activators and coactivators on transcription complex assembly [9].
• In vitro phosphorylation analysis showed a direct phosphorylation of CLK by CaMK II and p42 MAPK [extracellular signal-regulated kinase (ERK) 2], suggesting that these kinases regulate CLK/CYC-dependent transcription by direct phosphorylation of CLK [10].

Associations of e(y)1 with chemical compounds

• The e(y)1(ul) mutation, induced by the insertion of Stalker into the coding region, leads to the replacement of 25 carboxy-terminal amino acids by 17 amino acids encoded by the Stalker sequences and to a decrease of the e(y)1 transcription level [1].

Physical interactions of e(y)1

• GAGA factor and the TFIID complex collaborate in generating an open chromatin structure at the Drosophila melanogaster hsp26 promoter [11].
• Chromatin immunoprecipitation experiments show that the decrease in TFIID binding does not reduce GAGA factor binding [11].

Other interactions of e(y)1

• Sequence similarities between p62/p42 and the histones H4/H3, respectively, suggest that these subunits have a functional relationship with chromatin [12].
• We developed an approach called protease footprinting in which the broad-specificity proteases chymotrypsin and alkaline protease were used to probe binding of 32P-end-labeled TFIIB to GAL4-VP16 or TAF40 [9].

Analytical, diagnostic and therapeutic context of e(y)1

• Molecular cloning of Drosophila TFIID subunits [12].
• Both genetic and biochemical experiments demonstrate an interaction between e(y)2 and TAF(II)40, while immunoprecipitation studies demonstrate that the major complex, including both proteins, appears to be distinct from TFIID [7].
• In addition, affinity chromatography indicated a direct binding of the basal factor TFIIB to immobilized dTAFII40 [13].

References