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Transcriptional Networks BINDING SITES: TRANSCRIPTION FACTORS BIND TO THESE. MAY INDUCE AND MAY REPRESS. Compare Expression Time 1 GGCGAC CAGGTA Time 2 CCCAAC ACGGGC CACAAA Time 3 CAGGTA CACAAA CACAAA Time 4 CGTTAA CAGGTA CACAAA Time 3 Time 4 A AA A B B BB D D Time 1 C Time 2 C D F Correlation Time 1 Time 2 Time 3 Time 4 TF A AA A B B BB D D C C D F F Correlation:Find the highest correlations between expression level of TF of interest (red) and number of cis-element occurrence (normalized). AA means high numbers of A. ARTIFICIAL PROMOTERS T1 T2 B1, B2 CANDIDATES FOR BINDING B3, B4, B2 ARTIFICIAL PROMOTER: B1 B3 B4 If find expression, then B2 is out and T1 binds to B1 for sure. Preliminary Testing Preliminary Algorithm Results: Ndt80 binds to... Ndt80 binds to... 7 time points Cis-element 14 time points Cis-element 1. TCGCGA 2. TAAACT 3. CTAGAT 4. CACAAA** TCGCGA 1. --AACT(TA) CTAGAT 2. CACAAA** Out of 4,096 possible candidate cis-elements **Documented binding site (see below) Documented Binding Site: AAAA Ndt80 (TF) CACAAA MSE (cis-element) Documentation: promoter analysis, reporter constructs, and binding assays (Chu and Herskowitz, Cell 1998) Additional Results meiosis specific sites CACAAA - MSE SITE(Ndt80 binds) GGCGGC - URS SITE CCCCTT - LATE SPORULATION mitotic sites GCGCGC ACGCGT ACGCGG TGTGG CGCGAA - G1 PHASE CCACA - G1 PHASE GCAG - G2 PHASE diauxic shift ACTAA- Additional Results TRANSFAC-List of putative regulatory elements for specific genes. Algorithm results list of putative ciselements SEARCH ALL YEAST CIS-ELEMENTS IN TRANSFAC HIT RATE<10% YEAST CIS-ELEMENTS IN TRANSFAC ON GENES UP OR DOWN REGULATED IN SPORULATION HIT RATE<70% Rosetta Dataset Results: •microarray expession of 300 yeast deletion lines plus several drug treatments TF Algorithm Prediction Documented Binding Site GCN4 BAS1 1. TGAGTC 1. GAGTCA TGANTN* GAGTCA* *close to reverse complements 8 other TFs share the binding site Most involved in amino acid biosynthesis Create Data Sets 1.Compile data: sets of expressed transcription factors Time 2 Time 1 Time 3 Time 4 2. Retrieve regulatory sequences 2,000 bp CAGGCACAAATCTTACGTTATA... (CAGGCA) (A) (AGGCAC) (B) (GGCACA) (C) AAAA 3. Scan regulatory regions of expressed genes. Compile a set of potential cis-elements (C) (A)(B) Time 1 Time 2 Time 3 Time 4 Minimal Set Time 3 Time 4 A AA A B B BB D D Time 1 Time 2 TF C D F F B. Minimal Set. Find time point where 1) TF of interest (red) is present. 2)contains the fewest # of cis-elements. Eliminate ciselement candidates absent from this time point Transcriptional Networks Induction •Specificity •Modularity AAAA AAAA AAAA e.g. cis-element AAAA AAAA AAAA Repression AAAA AAAA Time 1 Time 2 AAAA Time 3