The alpha A-crystallin gene: conserved features of the 5'-flanking regions in human, mouse, and chicken.

Approximately 2 kb of 5'-flanking sequences of the lens-specific alpha A-crystallin genes from human and mouse are presented and compared with similar regions of the chicken gene. A repetitive element was found approximately 1 kb upstream from the coding sequences of the alpha A-crystallin gene in all three species (Alu in human, B2 in mouse, and CR1 in chicken), suggesting that they may have an important functional or structural role. Despite the ability of alpha A-crystallin promoters to function across species, dot matrix analyses show only limited similarity among the 600 bp 5' to the structural genes of these three species. The human 5'-flanking sequence is more similar to that of the mouse and chicken than the mouse and chicken are to each other. Numerous short sequences (8-13 bp) are common to all three genes but are distributed differently in each species. The locations and conservation of these sequence motifs suggest functional roles, possibly as cis-regulatory elements of transcription. One motif is similar to the alpha A-CRYBP1 binding site implicated earlier in the transcriptional regulation of the mouse alpha A-crystallin gene, and other motifs correspond to sites previously mapped by methylation interference studies in the mouse alpha A-crystallin promoter. The modular arrangement of conserved sequence motifs is consistent with evolutionary changes occurring at the level of gene regulation.