Characterization of bovine FUT7 furthers understanding of FUT7 evolution in mammals

Abstract

BackgroundThe Sialyl-Lewis X (Slex) is a well-known glycan structure involved in leukocyte homing and recruitment to inflammatory sites. SLex is well conserved among species and is mainly synthesized by FucT-VII in vertebrates. The enzyme responsible for its biosynthesis in cattle was not known.ResultsWe cloned a cDNA sequence encoding bovine α3-fucosyltransferase VII that shares 83% identity with its human counterpart. Located at the BTA 11 telomeric region, the 1029 bp open reading frame is spread over two different exons, E1 which also contains the unique 5’-untranslated region and E2 which includes the entire 3’-untranslated region. The bfut7 expression pattern is restricted to thymus and spleen. A single transcript leading to the synthesis of a 342 aa protein was identified. The encoded fucosyltransferase, produced as a recombinant enzyme in COS-1 cells, was shown to be specifically responsible for SLex synthesis in cattle. In addition, we showed that the gene promoter evolved from fish to mammals towards a complex system related to the immune system. But beyond the fact that the gene regulation seems to be conserved among mammals, we also identified 7 SNPs including 3 missense mutations in the coding region in a small panel of animals.ConclusionsThe FUT7 sequence was highly conserved as well as the specific activity of the encoded protein FucT-VII. In addition, our in silico promoter analysis and the high rate of polymorphism suggested that its function is evolving toward a complex system related to the immune system. Furthermore, comparing bovine to human and mouse sequences, it appeared that a decrease in gene regulation was correlated with an increase in mutation rate and wider tissue expression.

Integrative View of α2,3-Sialyltransferases (ST3Gal) Molecular and Functional Evolution in Deuterostomes: Significance of Lineage-Specific Losses

“…It would be informative to investigate evolution of Cis -acting region and regulatory elements controlling expression of these st3gal genes during vertebrates’ evolution. We predict series of transcription factor-binding sites losses in teleosts and gains in mammals, as it has been described previously for FUT7 ( Laporte et al 2012 ).…”

Development of a Bioinformatics Framework for Identification and Validation of Genomic Biomarkers and Key Immunopathology Processes and Controllers in Infectious and Non-infectious Severe Inflammatory Response Syndrome

“…These associations would suggest that this hub entity may play a key role in immunosuppressive cell functions (132), as its effect on many entities in the overarching pathways map is inhibitory (Figure 2). FUT7 [α1,3fucosyltransferase (Slex)] is involved in leukocyte/endothelial adhesion (216) in response to IL1β stimulation (217) and its involvement implies activation and binding of cells as part of the functionality associated with this hub entity in adults. CD58, a ligand of the T lymphocyte CD2 protein, which functions in adhesion and activation of T lymphocytes (218-220) was found to be associated with SLC16A3 by similar entities analysis and this may be of significance in that engagement of this key receptor with CD2 is predominant in chronic antigen stimulation, which may be an important feature of sepsis, particularly with regard to natural killer cell (NK) cell dysfunction (221).…”