Transcriptional and structural impact of TATA-initiation site spacing in mammalian core promoters.
BACKGROUND
The TATA box, one of the most well studied core promoter elements, is associated with induced, context-specific expression. The lack of precise transcription start site (TSS) locations linked with expression information has impeded genome-wide characterization of the interaction between TATA and the pre-initiation complex.


RESULTS
Using a comprehensive set of 5.66 x 10(6) sequenced 5' cDNA ends from diverse tissues mapped to the mouse genome, we found that the TATA-TSS distance is correlated with the tissue specificity of the downstream transcript. To achieve tissue-specific regulation, the TATA box position relative to the TSS is constrained to a narrow window (-32 to -29), where positions -31 and -30 are the optimal positions for achieving high tissue specificity. Slightly larger spacings can be accommodated only when there is no optimally spaced initiation signal; in contrast, the TATA box like motifs found downstream of position -28 are generally nonfunctional. The strength of the TATA binding protein-DNA interaction plays a subordinate role to spacing in terms of tissue specificity. Furthermore, promoters with different TATA-TSS spacings have distinct features in terms of consensus sequence around the initiation site and distribution of alternative TSSs. Unexpectedly, promoters that have two dominant, consecutive TSSs are TATA depleted and have a novel GGG initiation site consensus.


CONCLUSIONS
In this report we present the most comprehensive characterization of TATA-TSS spacing and functionality to date. The coupling of spacing to tissue specificity at the transcriptome level provides important clues as to the function of core promoters and the choice of TSS by the pre-initiation complex.
Ponjavic
Jasmina
J
Genome Exploration Research Group (Genome Network Project Core Group), RIKEN Genomic Sciences Center, RIKEN Yokohama Institute, Yokohama, Kanagawa, 230-0045, Japan. jasmina.ponjavic@anat.ox.ac.uk
Lenhard
Boris
B
Kai
Chikatoshi
C
Kawai
Jun
J
Carninci
Piero
P
Hayashizaki
Yoshihide
Y
Sandelin
Albin
A
D000818:Animals; D003198:Computer Simulation; D020224:Expressed Sequence Tags / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D015723:Gene Library; D023281:Genomics; D051379:Mice; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016385:TATA Box / Q000235:genetics*; D024363:Transcription Initiation Site