The helix-loop-helix transcription factor SEF-2 regulates the activity of a novel initiator element in the promoter of the human somatostatin receptor II gene.

Abstract

The effects of somatostatin hormones are mediated by a family of five different seven‐helix transmembrane spanning receptors (SSTR1–5). The expression of the five different SSTR subtypes displays a complex temporal‐ and tissue‐specific pattern. To investigate the molecular mechanisms controlling the different expression patterns of the SSTRs, we cloned the 5′‐flanking region of the human SSTR2 gene. Characterization of the SSTR2 promoter resulted in the identification of a novel initiator element (SSTR2inr). Transcriptional activity of the SSTR2inr is dependent on the presence of a binding site (E‐box) for basic helix‐loop‐helix (bHLH) transcription factors. By screening a mouse brain cDNA expression library we isolated a cDNA coding for the bHLH transcription factor SEF‐2. SEF‐2 binds to the E‐box present in the SSTR2inr, both in vitro and in vivo and activates transcription from the SSTR2inr. A single point mutation within the E‐box eliminates binding of SEF‐2 and results in a complete loss of transcriptional activity of the SSTR2inr. Furthermore, DNA binding studies demonstrate that the basal transcription factor TFIIB can be tethered to the SSTR2inr through physical interaction with SEF‐2. In summary, the SSTR2inr represents a novel type of initiator element that confers gene expression in the absence of a TATA‐box or binding sites for other known initiator factors, like YY‐1 or USF.

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

“…On the other hand, in other genes where an initiator-binding site has been functionally detected no motif resembling a conserved site is apparent (e.g. see [29]). A number of studies have identified various proteins as binding at or near the initiator motif, such as RNA polymerase II [3], YY1 [30], E2f(HIP1) [5], TAFII150 [1], USF [6], TFIIA [7], TFII-I [8,9] or TFIID itself [10][11][12], but the actual mechanisms of joint interaction of these proteins with the initiator (binding protein) and TFIID are obscure.…”

A Splice Variant of E2–2 Basic Helix-Loop-Helix Protein Represses the Brain-specific Fibroblast Growth Factor 1 Promoter through the Binding to an Imperfect E-box

“…spliced forms of E2-2 proteins, with and without RSRS, are known to be expressed in different cells (23,24,33,34). The three cDNA clones (VL1, VL2, and VL3) isolated from human brain stem cDNA library represent the splice variant of E2-2 containing RSRS (Fig.…”

“…1). However, an E2-2 cDNA that lacks the sequence encoding RSRS was isolated from a murine brain cDNA library (33). Hence, the potential presence of both spliced 2, 7, and 12) or B (Ϫ484 to Ϫ467) (lanes 3, 8, and 13).…”

Association of Transcription Factor 4 (TCF4) variants with schizophrenia and intellectual disability

“…Ostensibly using in vitro assays, it was shown that TCF4 could bind and activate gene expression at the conserved E-box (Ephrussi-box, 5'-CANNTG) containing sequences in the enhancers or promoter regions of several genes [17,[29][30][31][32]. Although TCF4 has been shown to regulate gene expression at both canonical and synthetic promoters and enhancers, surprising little is known about TCF4's genomic targets.…”

“…Intriguingly, TCF4-B has also been found to be a transcriptional repressor in different cell types [33][34][35]. However, it has been demonstrated that this isoform can also activate transcription in vitro, and therefore its function is highly context-dependent [30,36,37].…”