Two DNA sequence elements are known to recur frequently upstream of eulcaryotic polymerase II-transcribed genes. The TATAAA, at position -40, specifies the transcription initiation site. The GGCCAATCT is less frequent around -80. Sequence analysis of upstream regions reveals that the underlined yeast UAS2 consensus sequence, TGA1TGGT, is also very frequent at - 80 in higher polymerase II-transcribed animal sequences. The underlined CCAAT box and yeast UAS sequences are complementary. Structural analysis suggests some symmetry in their DNA structures. Upstream of the TATA-AT-rich region there is an abundance of GC seqeunces. Analysis of nucleotide tracts indicates that these are preferentially flanked by their complementary nucleotides with a pyrimidine-purine junction, i.e., TTAN, CCGn CnGG, TnAA. Here, I discuss DNA structrual considerations in upstream regions along with protein readout of the major and minor groove information content. These sequence-structure aspects are put in the general context of protein (factors)-DNA (elements) recognition and regulation. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.