Our laboratory studies transcription factors of higher eukaryotes. Transcription coactivator SAYP has been previously described in our laboratory. This factor has been found to function in many tissues during all developmental stages of drosophila and has homologues among all metazoans. PHF10, the human homologue of SAYP, has been proved to be indispensable for cell proliferation and associated with tumorogenesis. Mutations in gene encoding SAYP lead to decrease in viability, malfunction of cell cycle and organs development (Shidlovskii et al., EMBO J., 24: 97-107, 2005). SAYP acts as a component of stable coactivator supercomplex BTFly which also includes chromatin remodeler Brahma and general transcription factor TFIID (Vorobyeva et al., Proc. Natl. Acad. Sci. U S A, 106: 11049-54, 2009).
Critical role of SAYP in JAK/STAT signaling pathway and ecdysone cascade activation has been proved by experiments in our laboratory (Vorobyeva et al., Cell Cycle, 10: 1821-7, 2011; Panov et al, Nucleic Acids Res., 40: 2445-53, 2011). According to our model of SAYP action, gene-specific activators bound to promoters interact with BTFly which in turn recruits RNA-polymerase II (Pol II). Moreover, there have been data about participation of SAYP in drosophila immune system.
IMD is a signaling pathway which acts in response to bacterial infection in drosophila. Its action results in synthesis of special antimicrobial peptides (AMPs) required to neutralize microorganisms. We demonstrated that SAYP and components of Brahma and TFIID complexes are recruited onto AMP genes upon IMD pathway activation. SAYP may be important for increased secondary immune response: cell culture with SAYP knockdown showed weaker secondary response.
Also we demonstrated that SAYP can be associated with apparatus of 3’-processing of transcripts. We showed direct interaction of SAYP with this apparatus, as well as its recruitment onto AMPs genes upon IMD-pathway activation.
Thus we suppose that SAYP can effect gene expression by different mechanisms. First - it activates transcription by recruiting Pol II onto promoters, second - it interacts with mRNA processing machinery, and third - it can be recruited onto promoter during initial gene activation where it waits to activate the gene again. Moreover, SAYP is supposed to be a universal transcription factor for many signaling pathways, such as Toll, Wnt, Hedgehog, Ran and Ras.