Evolutionary Strategies for the Elucidation ofcisandtransFactors That Regulate the Developmental Switching Programs of the β-like Globin Genes

Deborah L. Gumucio, David A. Shelton, Wei Zhu, David Millinoff, Todd Gray, Jeffrey H. Bock, Jerry L. Slightom, Morris Goodman
1996 Molecular Phylogenetics and Evolution  
like globin genes were determined (Collins and Weiss-We describe three strategies for the identification of man, 1984). Sequences of the β globin clusters in specific cis and trans factors that regulate globin gene additional mammals (rabbit, mouse, goat, and galago) expression, all three of which are based on the evolufollowed, providing the basis for a molecular undertion of the globin genes and their expression patterns. standing of the structural evolution of the cluster. As The first
more » ... As The first approach, phylogenetic footprinting, relies sequences from additional species were gathered, the on a search for sequence similarities and is designed β-like globin locus became a valuable tool for the estabto elucidate the factors that control those expression lishment of phylogenetic relationships. patterns which are shared by orthologous globin genes Interest in another aspect of the globin genes, the of all eutherian mammals (e.g., the expression of the regulation of their developmental stage-specific expresglobin genes in the embryonic yolk sac and its repression patterns, began with descriptions of the changing sion in fetal and adult hematopoietic tissues). The seccomposition of the hemoglobin molecule during develond approach, differential phylogenetic footprinting, opment as assessed by electrophoretic separation of the relies on a search for sequence differences. This apvarious globin chains (Bunn and Forget, 1986). It soon proach may be of value in identifying the mechanisms became clear that each globin gene is expressed in a underlying the generation of novel expression patrestricted developmental stage and that these expresterns in specific lineages (e.g., the expression of ␥ as a sion patterns are tightly regulated. Coalescence of exfetal gene in the simian primates in contrast with the pression studies on the RNA and protein level with the embryonic expression of ␥ in all other mammals). Fistructural studies of the β-like globin locus soon estabnally, motif-based phylogenetic analysis takes into lished that the five active genes of the human β globin consideration the fact that many transcription factors cluster are arranged on the chromosome in the order are quite flexible in the recognition of their cognate sites. The approach allows the detection of function-of their developmental expression (Fig. 1A) . The most ally conserved binding sites despite their sequence 5′ gene in the human cluster, ε, is expressed in early variation.
doi:10.1006/mpev.1996.0004 pmid:8673285 fatcat:vs2uhthtjfc4vb7hrwj3mmr2q4