The TRANSFAC ® System comprises 7 databases: TRANSFAC ® Professional Suite TRANSFAC ® Professional Transcription factor database TRANSCompel ® Professional Composite elements database PathoDB ® Professional Pathologically altered transcription factors TRANSPRO™ Professional Collection of human promoter sequences S/MARt DB™ Professional Scaffold or Matrix Attached Regions databases Cytomer ® Ontology of cells, structures, organs TRANSPATH ® Professional Signal transduction pathways
One function – many structures (There‘s more then one way to do it) One structure – many functions (Multipurpose structure of promoters) Composite modules
organ, tissue, cell stage of development cell cycle phase extracellular signals Composite modules encode gene expression pattern
human TNF promoter mast cells T-cells + ? dendritic cells T-cells NFAT AP-1 NF-kB C/EBP AP-1 VDR
gherllojunomd-bype Genny fasltow Several regulatory messages could be written in the same sequence. Reading of the messages depends on the cellular context 1) 2) 3)
Composite modules w... Start of transcription... Parameters of the model to be estimated K - number of TF matrixes
Extract promoters from TRANSPRO Run TRANSPLORER Run CMFinder (Composite Module Finder) Select matrices Find corresponding TFs in TRANSFAC Run ArrayAnalyser in TRANSPATH to find key molecules Composite modules
Search for most probable binding sites regulating gene expression
Fuzzy puzzle hypothesis of the multipurpose structure of the eukaryotic promoters: of coding multiple regulatory messages in the same DNA sequence. A,B,C and D,E,F – two sets of TF; 1,2 – two sites in DNA; BC – basal complex.