gcn4 - Whole-genome analysis of GCN4 binding in...

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Whole-genome analysis of GCN4 binding in S.cerevisiae Gcn4/DNA diagram (CREB symmetric site and AP-1 asymmetric site: Song Tan, 1999) removed for copyright reasons. Lillian Dai Alex Mallet
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What is GCN4 ? ± S.cerevisiae transcription factor ± Primary regulator of the transcriptional response to amino acid starvation ± Has well-known binding motif: TGAsTCa* { Based on examining intergenic sequences ± Is known to bind both in intergenic regions and in ORFs** * ”Transcriptional Regulatory Code of A Eukaryotic Genome” , Harbison et al, Nature, Sep 2004 ** ”Gcn4 occupancy of open reading frame regions […]” , Topalidou et al, EMBO, 4(9) 2003
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Our project ± Investigating differences in GCN4 binding in intergenic regions versus ORFs { Does it bind to a different motif ? { How often do motifs occur in both types of regions ? { Are there differences in motif strength between intergenic regions and ORFs ? { How strongly does GCN4 bind in the different regions ? ± Similar to other studies eg Lieb et al* looked at Rap1 binding * ”Promoter-specific binding of Rap1 revealed by genome-wide maps of protein-DNA association”, Lieb et al, Nature Genetics 28 (2001)
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Dataset ± Whole-genome ChIP-ChIP binding data for GCN4 in S. cerevisiae from Gifford/Young lab under amino acid starvation conditions { Probes located (approx.) 300 basepairs apart ± “Binding call” data from Gifford lab ± Annotated S.cerevisiae genome from the Saccharomyces Genome Database (SGD)
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MEME Algorithm ± One Occurrence Per Sequence ( OOPS ) ± Zero or One Occurrence Per Sequence ( ZOOPS ) prior probability of a sequence containing a motif sequence ,1 , , , , ... ... ... ... A AA w GG G w TT T w CC C w BP P P P P θ ⎡⎤ ⎢⎥ = ⎣⎦ wm e r γ Procedure: E-step: compute M-step: solve () (,) [] t t ZX Z EZ φ = (1 ) argmax [logPr( , )] t t EX Z + = 12 { , ,..., } n X XX X = Input sequence 1 ij Z =
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This note was uploaded on 11/11/2011 for the course BIO 7.344 taught by Professor Bobsauer during the Spring '08 term at MIT.

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gcn4 - Whole-genome analysis of GCN4 binding in...

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