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1、Gene Expression Transcription RegulationDafna AradNoa Gordon20/5/02 Transcription Factors (TFs) Regulatory Motifs .TFregulatorymotifDNAgene , , : cis / trans / on/off DNA , - RNA Pol . ? ? ? ? Bucher P.:Regulatory elements and expression profilesCurr Opin Struct Biol 9 400-407 - . . . , . Bottom up

2、( ) ( )Top down . ( , ) Church GM: Computational Identification of Cis-regulatory Elements Associated with Groups of Functionally Related Genes in Saccharomyces cerevisiae J. Mol Biol 296 1205-1214 : AlignACE(Align nucleic Acid Conserved Elements) Gibbs Sampling algorithmAlignACE : . . . . .AlignACE

3、 , Regulon. : RNA - Clustering 5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATCGAAACATACAT5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATGACTCAACG5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT5- TGCGAACAAAAGAGTCATTACAA

4、CGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAATTGTCATGCATATGACTCATCCCGAACATGAAA5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTAGAGAAAAATAGAAAAGCAGAAAAAATAAATAA5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTCTTTTTTGGAAAGTGTGGCATGTGCTTCACACAAl

5、ignACE ExampleHIS7 ARO4ILV6THR4ARO1HOM2PRO3300-600 bp of upstream sequence per gene are searched in Saccharomyces cerevisiae.5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATCGAAACATACAT5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATGACTCAACG5- CACATCCAAC

6、GAATCACCTCACCGTTATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAATTGTCATGCATATGACTCATCCCGAACATGAAA5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTAGAGAAAAATAGAAAAGCAGAA

7、AAAATAAATAA5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTCTTTTTTGGAAAGTGTGGCATGTGCTTCACACAAAAAGAGTCAAAATGACTCAAAGTGAGTCAAAAAGAGTCAGGATGAGTCAAAATGAGTCAGAATGAGTCAAAAAGAGTCA* MAP score = 20.37 (maximum)HIS7 ARO4ILV6THR4ARO1HOM2PRO35- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATC

8、GAAACATACAT5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATGACTCAACG5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTA

9、AATTGTCATGCATATGACTCATCCCGAACATGAAA5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTAGAGAAAAATAGAAAAGCAGAAAAAATAAATAA*TGAAAAATTCGACATCGAAAGCACTTCGGCGAGTCATTACGTAAATTGTCCCACAGTCCGTGTGAAGCAC5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATCGAAACATACAT5- ATGGCAGAATCACTTTAAAACGTGGCCCC

10、ACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATGACTCAACG5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTCTTTTTTGGAAAGTGTGGCATGTGCTTCACACA*TGAAAAA

11、TTCGACATCGAAAGCACTTCGGCGAGTCATTACGTAAATTGTCCCACAGTCCGTGTGAAGCACMAP score = -10.0HIS7 ARO4ILV6THR4ARO1HOM2PRO35- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATCGAAACATACAT5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATGACTCAACG5- CACATCCAACGAATCACCTCACCGTT

12、ATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAATTGTCATGCATATGACTCATCCCGAACATGAAA5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTAGAGAAAAATAGAAAAGCAGAAAAAATAAATAA5- GG

13、CGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTCTTTTTTGGAAAGTGTGGCATGTGCTTCACACA*samplingTGAAAAATTCGACATCGAAAGCACTTCGGCGAGTCATTACGTAAATTGTCCCACAGTCCGTGTGAAGCACAdd?*TGAAAAATTCGACATCGAAAGCACTTCGGCGAGTCATTACGTAAATTGTCCCACAGTCCGTGTGAAGCACTCTCTCTCCAHIS7 ARO4ILV6THR4ARO1HOM2PRO3 2 -?alignments5- TCTCTCTCCACGG

14、CTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATCGAAACATACAT5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATGACTCAACG5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCA

15、TTTCTATC5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAATTGTCATGCATATGACTCATCCCGAACATGAAA5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTAGAGAAAAATAGAAAAGCAGAAAAAATAAATAA5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTCTTTTTTGGAAAGTGTGGCATGTGCTTCACACA*TGAAAAATTCGACATCGAAAGCACTTCGGCGAGTCATTACGTAAATTG

16、TCCCACAGTCCGTGTGAAGCACAdd?*TGAAAAATTCGACATCGAAAGCACTTCGGCGAGTCATTACGTAAATTGTCCCACAGTCCGTGTGAAGCACRemove.ATGAAAAAATHIS7 ARO4ILV6THR4ARO1HOM2PRO3 2 -?alignments5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATCGAAACATACAT5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGT

17、TACTGCGAAATGACTCAACG5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAATTGTCATGCATATGACTCATCCCGAACATGAAA5- ATTGATTGACTCATTTTCCTCTGACTACTACCAG

18、TTCAAAATGTTAGAGAAAAATAGAAAAGCAGAAAAAATAAATAA5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTCTTTTTTGGAAAGTGTGGCATGTGCTTCACACA*GACATCGAAAGCACTTCGGCGAGTCATTACGTAAATTGTCCCACAGTCCGTGTGAAGCAC* *GACATCGAAACGCACTTCGGCGGAGTCATTACAGTAAATTGTCACCACAGTCCGCTGTGAAGCACAHIS7 ARO4ILV6THR4ARO1HOM2PRO3 2 -?alignments5

19、- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATCGAAACATACAT5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATGACTCAACG5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGA

20、CAAAATGTATAGTCATTTCTATC5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAATTGTCATGCATATGACTCATCCCGAACATGAAA5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTAGAGAAAAATAGAAAAGCAGAAAAAATAAATAA5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTCTTTTTTGGAAAGTGTGGCATGTGCTTCACACAAAAAGAGTCAAAATGACTCAAAGTGAGTCAAAAA

21、GAGTCAGGATGAGTCAAAATGAGTCAGAATGAGTCAAAAAGAGTCA* MAP score = 20.37 (maximum)HIS7 ARO4ILV6THR4ARO1HOM2PRO35- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAXAGTCAGACATCGAAACATACAT5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATXACTCAACG5- CACATCCAACGAATCACCTCACCGTTATCGT

22、GACTXACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT5- TGCGAACAAAAXAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAATTGTCATGCATATGACTXATCCCGAACATGAAA5- ATTGATTGACTXATTTTCCTCTGACTACTACCAGTTCAAAATGTTAGAGAAAAATAGAAAAGCAGAAAAAATAAATAA5- GGCGCCA

23、CAGTCCGCGTTTGGTTATCCGGCTGACTXATTCTGACTXTTTTTTGGAAAGTGTGGCATGTGCTTCACACAAAAAGAGTCAAAATGACTCAAAGTGAGTCAAAAAGAGTCAGGATGAGTCAAAATGAGTCAGAATGAGTCAAAAAGAGTCA*maskingHIS7 ARO4ILV6THR4ARO1HOM2PRO3 . . sampling . MAP ScoreMaximum a priori log likelihood .MAP Score = N log R :N - .R - , : -1000 , 10 -2000 5=R

24、. MAP Score MAP Score :N ( ) . . . AlignACE :248 . 29 . false positive ORFs AlignACE () 3311 . :Group specificityPositional biasGroup Specificity Score MAP Score , . A-rich motifs .Group Specificity Score (ScanACE ). , . ScanACE . AlignACE . , .Positional Bias ( ScanACE) . .Clustering CompareACE. clustering 6 . 1 - 1- -1 . AlignACE () AlignACE () , - clustering 54 , -25 . AlignACE . . S12 RRPE - positional bias . rRM

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