Abstract
Core promoter regions of protein-coding genes in metazoan genomes are structurally highly diverse and can contain several distinct core promoter elements, which direct accurate transcription initiation and determine basal promoter strength. Diversity in core promoter structure is an important aspect of transcription regulation in metazoans as it provides a basis for gene-selective function of activators and repressors. The basal activity of TATA box-containing promoters is dramatically enhanced by the initiator element (INR), which can function in concert with the TATA box in a synergistic manner. Here we report that a functional INR provides resistance to NC2 (Dr1/DRAP1), a general repressor of TATA promoters. INR-mediated resistance to NC2 is established during transcription initiation complex assembly and requires TBP-associated factors (TAFs) and TAF- and INR-dependent cofactor activity. Remarkably, the INR appears to stimulate TATA-dependent transcription similar to activators by strongly enhancing recruitment of TFIIA and TFIIB and, at the same time, by compromising NC2 binding.
Highlights
Dent) levels of accurate transcription initiation in vitro [1, 2]
Core promoter elements identified to date include the TATA box (TATA), the initiator element (INR), TFIIB recognition elements (BREs), the downstream promoter element (DPE), the motif-ten element (MTE), and the downstream core element (DCE) [1, 2]
A murine terminal deoxynucleotidyl transferase (mTdT)-TATA/INR variant was obtained by introducing a consensus TATA box between positions Ϫ31 and Ϫ25 using site-directed mutagenesis [22]
Summary
Dent) levels of accurate transcription initiation in vitro [1, 2]. Metazoan core promoters can contain several distinct core promoter sequence elements, which direct functional PIC assembly and transcription start site selection and which determine basal promoter strength [1, 2]. At higher NE protein concentrations supporting INR stimulation of basal transcription levels, depletion of NC2 selectively increased transcription from TATA-only promoter templates, but had comparatively little effect on the activity of the corresponding TATA/INR variants (Fig. 1, compare lanes 2– 4 with lanes 6 – 8; Fig. 2A, lanes 6 and 7; Fig. 2B, lanes 1 and 2).
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