Book of Abstracts: Albany 2007
June 19-23 2007
Binary DNA Tracts as Transcription Control Elements
We have been identifying a new element in gene promoters, which suggests a novel level of gene transcription regulation -- control via DNA Topology. We have previously documented that in eukaryotic gene promoters, from yeast to human, there is a huge excess of long DNAs tracts (>12nt) composed of only two of the bases ("Binary DNA"). We find now (1) that in promoters, overrepresentation of binary tracts is even higher. The most overrepresented binary motifs are purines on one strand, with pyrimidines on the complementary one ("R.Y tracts"), as well as the auto-complementary ("AT rich") motif. A third motif, G,T on one strand, complemented by A,C, is the leading overrepresented binary motif in drosophila. The overrepresented R.Y tracts concentrate in the first 200 bases 5' to the Transcription Start Site (TSS), while the excessive W tracts tend to concentrate farther upstream.
We have proposed that the overrepresented long DNA tracts represent DNA unwinding elements, elements that participate somehow in the process of gene activation. In support of that notion, we have examined the promoters of two yeast genes (DED1 and CYC1) that contain long pyrimidine tracts in their promoters (2). Single-strand probing of supercoiled plasmids containing these promoters by specific nuclease P1 and by permanganate, as well as topological analysis, all show that these regions can assume an unwound state. Similar observations have been reported from quite a number of laboratories, supporting the existence of unwound DNA regions in gene promoters.
We have now examined the occurrence of binary DNA tracts also at the gene terminator regions, at the 3' ends . An even higher level of overrepresentation of binary DNA tracts >12nt was documented at the 3' end of several chromosomes, from yeast to man. This suggests a model by which an unwound DNA region at the 3' end is transferred back to the 5' end of the gene by a supercoiling -- desupercoiling mechanism; this mechanism facilitates the reentry of a batch of RNA polymerases at the gene promoter region, by direct transloading from the unwound terminator to the promoter region. The nature and size of the transferred unwound region can determine the levels of initiation of gene transcription, thus providing an additional mode for the control of gene expression.
References and Footnotes
Dept. of Molecular Cell Biology