JUNK DNA AND SECTORIAL GENE REPRESSION

Transcriptional repression in eukaryotes often involves tens or hundre ds of kilobase pairs, two to three orders of magnitude more than the b acterial operator/repressor model does. Classical repression, represen ted by this model, was maintained over the whole span of evolution und er different guises, and consists of repressor factors interacting pri marily with promoters and, in later evolution, also with enhancers. Th e use of much larger amounts of DNA in the other mode of repression, h ere called the sectorial mode ('superrepression'), results in the conc eptual transfer of so-called junk DNA to the domain of functional DNA. This contribution to the solution of the c-value paradox involves per haps 15% of genomic 'junk,' and encompasses the bulk of the introns, t hought to fill a stabilizing role in sectorially repressed chromatin s tructures. In the case of developmental genes, such structures appear to be heterochromatoid in character. However, solid clues regarding ge neral structural features of superrepressed terminal differentiation g enes remain elusive. The competition among superrepressible DNA. secto rs for sectorially binding factors offers, in principle, a molecular m echanism for developmental switches. Position effect variegation may b e considered an abnormal manifestation of normal processes that underl y development and involve heterochromatoid sectorial repression, which is apparently required for local elimination or modulation of morphol ogical features (morpholysis). Sectorial repression of genes participa ting either in development or in terminal differentiation is considere d instrumental in establishing stable cell types, and provides a basis for the distinction between determination and cell type specification . The gamut of possible stable cell types may have been broadened by t he appearance in evolution of heavy isochores. Additional types of rel atively frequent GC-rich cis-acting DNA motifs may offer reiterated bi nding sites to factors endowed with a selective (though not individual ly strong) affinity for these motifs. The majority of sequence motifs thought to be used in superrepression need not be individually maintai ned by natural selection. It is re-emphasized that the dispensability of sequences is not an indicator of their nonfunctionality and that in many cases, along noncoding sequences, nucleotides tend to fill funct ions collectively, rather than individually. (C) 1997 Elsevier Science B.V.