DNA bend sites in the human beta-globin locus: evidence for a basic and universal structural component of genomic DNA.

Here we summarize the DNA bend sites in a 66-kb region of the human beta-globin locus. A total of 98 sites were mapped by circular permutation assay along the locus with an average interval of 679.2 +/- 229.6 bp between them. The distribution of the bend sites indicated that although the most frequent distance was about 650-700 bp, there appeared to be preferences at 300-400, 500-550, 800-850, 1,000-1,050, and 1,150-1,200 bp, indicating that these distances are multimers of a 170-bp basic unit. DNA bend sites in the globin-encoding regions indicated that most of their locations relative to the cap sites were conserved during evolution. Insertion of Alu and L1 sequences that occurred at various times and changed the distances of the sites was corrected for the epsilon-, psi beta-, and delta-globin genes. The only exception of the conservation was observed at the duplication junctions of the two gamma-globin genes, which occurred 25-35 MYA. Among the 75 A/A/A (A2N8A2N8A2) sequences found in the 51 bend sites, 59 sequences from 47 sites showed bending profiles by oligonucleotide-based assay. All of these sites were included in the sites predicted by computer analysis based on the distribution of AA and TT dinucleotides. These lines of evidence suggest that these DNA bend sites are one of the basic structural components universally present in genomic DNA.