TGF-β in tolerance, development and regulation of immunity.

The TGF-β superfamily is an ancient metazoan protein class which cuts across cell and tissue differentiation, developmental biology and immunology. Its many members are regulated at multiple levels from intricate control of gene transcription, post-translational processing and activation, and signaling through overlapping receptor structures and downstream intracellular messengers. We have been interested in TGF-β homologues firstly as key players in the induction of immunological tolerance, the topic so closely associated with Ray Owen.

Candidate Sertoli cell specific promoter element for a TGFbeta family member (Amh) and a 3' UTR enhancer/repressor for the same gene.

Comparison between 400 nt of mouse DNA sequence immediately upstream (5') of the coding sequence of the Sertoli cell expressed genes, Amh and Tsx, identified a 33 nt sequence with a significant identity: this was considered to be a candidate Sertoli specific regulatory element (SSRE). Another highly conserved sequence has been identified immediately downstream (3') of the Amh polyadenylation signal (DSRE). The action and specificity of these two putative regulatory elements, inserted into a reporter vector (pd2EGFP), has been investigated by transient transfection of mouse fibroblast and Sertoli cells.