Disease relevance of Transcription Initiation Site

• This location contrasts with the location of the operator in other phage or bacterial operons where the repressor binds more closely to the respective transcription initiation sites [1].
• Homologous sequences are present (i) in the cAMP-regulated rat tyrosine aminotransferase, prolactin, and phosphoenolpyruvate carboxykinase genes and (ii) 5' to the transcription initiation sites of cAMP-regulated Escherichia coli genes [2].
• Redefining the Epstein-Barr virus-encoded nuclear antigen EBNA-1 gene promoter and transcription initiation site in group I Burkitt lymphoma cell lines [3].
• The human epsilon-globin gene has a number of alternative transcription initiation sites which correspond with regions of DNase I hypersensitivity upstream of the canonical cap site [4].
• Furthermore, in murine erythroleukemia cells, overexpressed YY1 causes increased levels of c-myc mRNA initiated from both major transcription initiation sites of the endogenous c-myc gene [5].

High impact information on Transcription Initiation Site

• ER binds selectively to a limited number of sites, the majority of which are distant from the transcription start sites of regulated genes [6].
• Thus, SUA7 encodes a yeast TFIIB homolog and functions in transcription start site selection [7].
• The major determinant in the transcriptional control of class I genes of the major histocompatibility complex is an enhancer sequence located around -170 from the transcription start site, which binds a factor named KBF1 [8].
• Sequences downstream of the Antp P1 and Ultrabithorax transcription start sites mediate the observed activation [9].
• DNA sequencing, S1 mapping, and primer extension experiments have established that the transcription initiation site of the Factor B gene lies only 421 bp from the poly(A) site of the C2 gene [10].

Chemical compound and disease context of Transcription Initiation Site

• A region of 485 base pairs upstream from the transcription initiation site of the human cardiac actin gene directs high-level transient expression of the bacterial chloramphenicol acetyltransferase gene in differentiated myotubes of the mouse C2C12 muscle cell line, but not in mouse L fibroblast or rat PC-G2 pheochromocytoma cells [11].
• We have previously reported that the promoter region of the mouse interleukin-5 (IL-5) gene, extending from a nucleotide position about -1,200 to +33 relative to the transcription initiation site, can mediate transcriptional stimulation by phorbol 12-myristate 13-acetate and dibutyryl cAMP (Bt2cAMP) in mouse thymoma EL-4 cells [12].
• Using gene-manipulation techniques, we made a set of short insertions and deletions in the Escherichia coli galactose operon between the transcription start site and the Shine-Dalgarno sequence of the first gene of the operon, galE [13].
• In order to better understand the basis of this transcription-coupled repair we developed an in vitro system with purified transcription and nucleotide excision repair proteins and a plasmid containing the adenovirus major late promoter and a thymine dimer in the template strand downstream of the transcription start site [14].
• The human preproendothelin-1 mRNA contains a frequent adenine insertion polymorphism (allele frequency = 0.28) within the 5'-untranslated region (5'-UTR), 138 bp downstream of the transcription start site, which was assumed to be related to hypertension [15].

Biological context of Transcription Initiation Site

• In yeast (Saccharomyces cerevisiae), transcriptional activators, such as Gal4 and Gal4-VP16, work ordinarily from sites located in the upstream activating sequence (UAS) positioned about 250 base pairs upstream of the transcription start site [16].
• Activation by Tat requires a cis-acting element, the transactivation response (TAR) site, located immediately downstream of the transcription start site [17].
• Tat functions through a sequence known as TAR, located immediately downstream of the transcription start site in the long terminal repeat [18].
• Transcription-dependent DNA melting on the yeast GAL1 and GAL10 promoters was found to be more closely correlated with the TATA box than the transcription start site [19].
• The major fetal IGF-II promoter was defined in transient transfection assays as a region spanning from nucleotides -295 to +135, relative to the transcription start site [20].

Anatomical context of Transcription Initiation Site

• The PIE motif contains a consensus site for the macrophage and B cell transcription factor, PU.1, and is adjacent to the cluster of transcription start sites [21].
• The MB1 regulatory sequence of the myelin basic protein (MBP) gene spanning between nucleotides -14 to -50 with respect to the transcription start site is critical for cell type-specific transcription of the MBP gene, which encodes the major protein component of myelin sheath in cells derived from the central nervous system (CNS) [22].
• Hypersensitive site 1, present in the DU980 T-cell line, was located 4.5 kilobases upstream of the presumed CD7 transcription initiation site [23].
• Conversely, several CpG sites approximately 22 kb downstream of the transcription start site in intron 5 are preferentially methylated on the expressed paternal allele in somatic tissues and male germ cells, whereas these same sites are unmethylated in fetal oocytes [24].
• This transcript, which we have named PPEIA-3' RNA, hybridizes with probes directed at a region of PPE intron A downstream of an alternative germ-cell transcription start site, but does not contain PPE protein coding sequences [25].

Associations of Transcription Initiation Site with chemical compounds

• Analysis of a set of deletion mutants revealed that the minimum sequence required for cadmium regulation lies within 90 nucleotides of the transcription start site [26].
• Alanine tRNA synthetase represses transcription of its own gene by binding specifically to a palindromic sequence which flanks the gene's transcription start site [27].
• In the presence of adenosine triphosphate, the NtrC protein catalyzes isomerization of closed recognition complexes between sigma 54-holoenzyme and the glnA promoter to open complexes in which DNA in the region of the transcription start site is locally denatured [28].
• We report here that the mapping of single stranded DNA in vivo with potassium permanganate (KMnO4) and nuclear run-on transcription assays reveal that polymerase is paused near position +30 relative to the major c-myc transcription initiation site [29].
• As this gene is very closely spaced to the related Factor B gene [the C2 poly(A) site is only 421 bp from the transcription start site of Factor B] we have isolated this same intergenic sequence from four other mammals (mouse, cat, rabbit and cow) [30].

Gene context of Transcription Initiation Site

• Thus, the IL-2 inducibility of the IL-2Ralpha gene is unexpectedly mediated by two widely separated regulatory Stat5-dependent elements, located both upstream and downstream of the transcription initiation sites [31].
• Xite harbors intergenic transcription start sites and DNaseI hypersensitive sites with allelic differences [32].
• The location of E(z)- and Pc-containing complexes downstream of the Ubx transcription start site suggests that they may inhibit transcription by interfering with assembly of the preinitiation complex or by blocking transcription initiation or elongation [33].
• Chromatin immunoprecipitation (ChIP) assay identified a 500 bp region located 4 kb upstream of the HoxA9 transcription initiation site as a SUZ12 binding site, which responds to SUZ12 knockdown and might play an important role in regulating HoxA9 expression [34].
• However, the Rpb9 subpathway operates more effectively in the coding region than in the region upstream of the transcription start site, whereas the Rad26 subpathway operates equally in the two regions [35].

Analytical, diagnostic and therapeutic context of Transcription Initiation Site

• Sequence analysis revealed two sets of overlapping E2F-binding sites located between -12 and -40 relative to the transcription initiation site [36].
• Deletion of the genomic sequences encompassing the transcription initiation site and the entire coding regions of murine PAI-1 was demonstrated by Southern blot analysis [37].
• The glycine tRNA genes in silkworm Bombyx mori contain two regulatory regions upstream of the transcription start site as identified by direct transcription of 5' deletion mutants, transcription competition, gel mobility shift assays, and footprinting [38].
• Similarly to the mouse, analysis of cDNAs and Northern blots identified abundant testis-specific transcript isoforms generated by use of alternate transcription initiation sites [39].
• Reverse-transcriptase polymerase chain reaction showed expression of a unique hybrid IGH-BCL2 transcript involving the transcription initiation site I(mu) [40].

References