Human ribosomal DNA: novel sequence organization in a 4.5-kb region upstream from the promoter

We have investigated the molecular organization of a portion of the human ribosomal nontranscribed spacer, by determining the sequence of 4580 bp of DNA upstream from the promoter. This region contains two pairs of oppositely oriented Alu elements, each of which is separated by dA (or dT)-rich stretches. One dT-rich region extends over 800 bp and is of variable length in different ribosomal genes. This and other portions of the spacer consist of simple sequences reiterated many times: for instance, (TACAA)26, (TTTC)117, and (TTGC)47. We are able to position the distal junction of the ribosomal repeat and sequences that have the propensity to form alternate structures, such as Z-DNA and bent DNA. A complex DNA methylation pattern and the influence on transcription of analogous regions in other species, suggest that this upstream area may be important to the expression of the human gene.