Nucleotide quartets in the vicinity of eukaryotic transcriptional initiation sites: some DNA and chromatin structural implications.

Examination of all mammalian, nonmammalian vertebrate, and invertebrate genomic sequences present in the GenBank data shows a striking distribution of the G + C (A + T) content. It has been known for a few decades that the G + C content in higher organisms averages 42%. The average of the sequenced genomic regions is significantly higher, with a distinct peak near the transcription initiation site. This distribution, as well as the overall A + T genomic incidence may be directly related to DNA geometry. Specific A-T sequences may facilitate DNA curving, allowing more tight packaging of chromatin in eukaryotic genomes. To examine further which particular oligomers may potentially contribute to recognition of transcription initiation sites, an extensive search was instituted for detecting recurrences of particular oligonucleotides in the regions surrounding these sites. Accordingly, the analyzed mammalian genomic sequences have been scanned for the occurrences of each of the 256 quartets. The CAAT box components yield moderate peaks. As expected, the TATA box is much more pronounced, though the ATAA sequence yields a more striking peak than the TATA. Tetranucleotides containing solely A + T are relatively rare downstream from coding regions. Upstream, their level is low except for the distinct peaks; the level of A4 is very high upstream. All significant signals are enumerated. Of the G + C-rich quartets, CCCC and AGGG exhibit large peaks near transcription initiation sites. These may produce straight DNA segments.