Molecular Characterization of STAT5A- and STAT5B-Encoding Genes Reveals Extended Intragenic Sequence Homogeneity in Cattle and Mouse and Different Degrees of Divergent Evolution of Various Domains

Abstract

The STAT transcription factors form a family of signal transducers and activators of transcription. We sequenced the bovine STAT5B cDNA and both STAT5-encoding genes, STAT5A and STAT5B, representing the first complete description of any STAT5-encoding gene. DNA fiber FISH hybridization revealed that the genes reside only 40 kbp apart on BTA19. Both genes are segmented into 19 exons and all but two of the homologous exons are of equal size. The genes harbor a central block of nearly identical DNA sequence (97.5% sequence identity over 3373 bp), spanning from intron 5 to intron 9. Isolation and sequencing of the homologous segments from mouse revealed the same unusually high degree of intronic sequence conservation in these segments of the murine STAT5-encoding genes. However, the respective sequences are completely divergent between the two species. A comparison of the inter- and intragenic cDNA sequence preservation at nonsynonymous sites reveals that the DNA-binding domain is under the strongest selection pressure for both intergenic and factor-specific intragenic sequence preservation. The so-called "SH3" segment of the linker domain, in contrast, shows species-specific sequence identity in all but one amino acid residues in both factors, in cattle, human, and mouse. This indicates that the same species-specific selection pressure occurs on the linker domain from both factors, STAT5A and STAT5B. Thus, the comparison of evolutionary selection pressures resting on various domains suggests that the DNA-binding domain might contribute to differential DNA binding of STAT5A and STAT5B factors, while both might interact equally well with other cellular factors through a segment of the linker domain.

Signal Transduction Pathways Regulated by Prolactin and Src Result in Different Conformations of Activated Stat5b

“…It had been suggested that a single amino acid in the DNA binding region of Stat5a and Stat5B could confer distinct DNA binding specificities (46). However, it is now apparent that this amino acid change (E433G) does not even normally occur in murine Stat5b, and that the DNA binding domain, and especially the amino acid residues that contact the DNA helix, are highly conserved in Stat5a and Stat5b from all mammalian species studied to date (56). Not surprisingly, therefore, careful binding site selection studies performed with baculovirus-expressed Stat5a and Stat5b have generated identical consensus high affinity binding sites (47).…”

Polymorphism identification in goat DGAT1 and STAT5A genes and association with milk production traits

“…It is a key intracellular mediator of prolactin signaling and can activate transcription of milk protein genes in response to prolactin (Wakao et al, 1994). STAT5 exists in two isoforms -A and B, which differ by a few amino acids in the carboxylic end of the protein molecule; separate genes code both of them (Seyfert et al, 2000). In goat, the STAT5A gene was located at chromosome 19 (Goldammer et al, 1997).…”

DNA-remethylation around a STAT5-binding enhancer in the αS1-casein promoter is associated with abrupt shutdown of αS1-casein synthesis during acute mastitis

“…The cascade of factors and events transducing the prolactin signal via the JAK2/STAT5 pathway into the cell and resulting in stimulated expression of target genes has been well established during the last decade (Hennighausen et al 1997, Groner 2002. Ultimately, the cascade activates in the cytoplasm the closely related (Seyfert et al 2000) STAT5A and STAT5B transcription factors. After translocation into the nucleus, they bind to a conserved DNA sequence motif in target promoters, known as GAS sequence (TTCNNNGAA; Schindler et al 1995, Ehret et al 2001.…”