A -Acting DNA Element Located between TATA Box and Transcription Initiation Site Is Critical in Response to Regulatory Sequences in Human Angiotensinogen Gene

Abstract

The promoter of the human angiotensinogen (hAG) gene functioned in its own core promoter context but not when replaced with simian virus 40 (SV40) core promoter, suggesting the presence of a transcriptionally important cis-acting sequence. Electrophoretic mobility shift assays demonstrated that a ubiquitously expressed nuclear factor, AGCF1, bound to AGCE1 (hAG core promoter element 1; positions ؊25 to ؊1) located between the TATA box and transcription initiation site. Substitution mutation in AGCE1 which disrupted AGCF1 binding affected the promoter activity more severely than a nonsense mutation of the hAG TATA sequences did. When AGCE1 was placed at the downstream of SV40 core promoter, the responsiveness to hAG upstream region was significantly restored. Furthermore, mutation and in vivo competition experiments suggested that AGCF1 acts as a critical regulator of hAG transcription by mediating the activity of the hAG upstream and downstream enhancer elements. DNase I footprinting and UV cross-linking analyses showed that AGCF1 with apparent molecular masses of 31, 33, and 43 kDa as the components protected the region from ؊26 to ؊9 which partially overlapped with the TATA box consensus sequences. These findings indicate that AGCE1 in addition to the TATA box plays a key role in mediating the hAG regulatory elements.

The effect of genetic variation in angiotensinogen on serum levels and blood pressure: a comparison of Nigerians and US blacks

“…[34][35][36] Studies conducted on chimpanzees showed that when exposed to high salt diets their BP levels increase, which is consistent with adaptation to a low sodium environment. 37 This evidence supports the hypothesis that modern humans inherited from their ancestors a gene that was adaptive in an environment low in sodium.…”

“…27 However, when tests of selection are applied to the entire gene, no evidence of a selective sweep or any other form of selection is present. Furthermore, other sites, like the À217, À20 and À18 have been shown to affect basal transcription rates 34,36 and therefore the À6 position is just one among many that could influence the levels of gene expression.…”

Transcription of the juvenile hormone esterase gene under the control of both an initiator and AT-rich motif

“…The role and form of the TATA box are also more complicated than originally conceived. While in some yeast and human genes the canonical TATAAA motif can functionally survive mutation to other AT-rich arrays [14,19,31,32], in other genes, such mutations either abolish transcriptional function or move the start site [33,34]. There is also the situation in which a TATA box is present as the wild-type motif and can bind TBP or TFIID, but yet is dispensable for significant rates of transcription [35,36].…”

“…Although the binding of additional transcription factors to core promoters at sites other than the TATA box or initiator has been shown in other genes (e.g. AGCE1 binding at bp k26 to k9 of the angiotensinogen gene ; [14]), the results obtained here are distinguished from similar experiments with other TATA\initiator-containing core promoters, in which a third (or more) factor(s) was\were not sufficiently associated to the basal apparatus to dislodge it from a wild-type core (e.g. [52]).…”

“…There is increasing evidence that particular DNA sequences in the core promoter, other than the TBP-and initiator-binding motifs, play a pivotal role in controlling whether a particular TBP\TAFII complex [13] or other non-TFIID factor (e.g. see [14]) binds to the given core promoter. In some cases, hormone receptors may in fact bind at either the immediately proximal side of the TATA box or over the initiator site, sterically blocking transcription complexes from binding to the promoter [15][16][17][18].…”