Putative human CFTR regulatory domains. Relative positions of proposed human CFTR transcription regulatory sequences and their conservation between mammals. (A) CFTR Intron 9/exon 10 3′ splice site aligned in mouse, human, and Fugu. Bold type indicates blocks of sequence conserved between human and Fugu, but not in mouse. Italic sequence shows consensus branch-point and 3′ splice site sequences. The proposed branch-point A is marked with *. $ indicates the first nucleotide of exon 10. Capitalized letters of consensus sequences summarize positions where both Fugu and human match the consensus. (B) Alignments 1 to 4 illustrate the conservation of selected CFTR promoter elements between human (Homo sapiens), gibbon (Hylobates lar), monkey (Saimiri sciureus), cow (Bos taurus) and rabbit (Oryctolagus cuniculus) at coordinates relative to the start of translation of human CFTR. Asterisks indicated nucleotides conserved between all aligned species. Background shading marks the extent of proposed elements. (C) The relative position of sequence motifs implicated in CFTR regulation, DNase I hypersensitive sites, and exons one and two are indicated with respect to the translational start site (ATG). Annotated elements are as defined in: 1(), 2(), 3(), 4(), 5(), 6(). (D) FA and FB Fugu CFTR intron 1 elements are shown in alignment with the conserved human HA element. Asterisks indicate nucleotides conserved in all three elements. The 10-bp perfect palindromes of FB and HA are indicated by a horizontal bar, and the axis of symmetry is indicated by a vertical arrow. Horizontal arrows indicate partially conserved direct repeats in each element. The coordinates indicate distance from the 3′ end of CFTR exon 1. Background shading marks the extent of the proposed element.