motif_finding - 4. Finding Regulatory Motifs in DNA...

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Unformatted text preview: 4. Finding Regulatory Motifs in DNA Sequences (Chapter 4 and 12) Outline • Implanting Patterns in Random Text • Gene Regulation • Regulatory Motifs • The Motif Finding Problem • Brute Force Motif Finding • The Median String Problem • Search Trees • Branch-and-Bound Motif Search • Branch-and-Bound Median String Search • Consensus and Pattern Branching: Greedy Motif Search • PMS: Exhaustive Motif Search Identifying Motifs Every gene contains a regulatory region (RR) typically stretching 100-1000 bp upstream of the transcriptional start site Genes are turned on or off by regulatory proteins • These proteins bind to upstream regulatory regions of genes to either attract or block an RNA polymerase • Regulatory protein transcription factor (TF) binds to a short DNA sequence called a motif or (TFBS: transcription factor binding site) • So finding the same motif in multiple genes‟ regulatory regions suggests a regulatory relationship amongst those genes Identifying Motifs: Complications • We do not know the motif sequence • We do not know where it is located relative to the genes start • Motifs can differ slightly from one gene to the next • How to discern it from “random” motifs? Transcription Factor Binding Sites (TFBS) • A TFBS can be located anywhere within the Regulatory Region . • TFBS may vary slightly across different regulatory regions since non-essential bases could mutate Transcription for E.Coli The transcription process in reality even for a simple E.Coli is much more complex than what we have described. The process is divided into three phases: initiation, elongation and termination. Initiation: The RNA polymerase initiates the operation and it must transcribe not any arbitrary part of DNA but only the gene. For this the polymerase first „bind‟ to a location upstream of the gene. This site is called a promoter sequence. The promoter is a short DNA sequence which can be bind to the polymerase. In E.Coli, the promoter sequence consists of two distinct sequences at a distance -10 and -35 upstream from the position at which transcription starts. The actual sequences may vary from gene to gene but they are related to the following two consensus sequences both located in the non-template strand :-35 box 5’-TTGACA-3’-10 box 5’-TATAAT-3’ 5’ 3’ gene-10 box- 35 box 3’ 5’ gene-10 box- 35 box 5’ 3’ + 1- 10 + 1 RNA polymerase holoenzyme Sigma subunit Closed promoter complex Open promoter complex Initiation: First two ribonucletides-35 Core enzyme Elongation 3’ 5’ 5’ RNA Transcript Direction of transcription + 1 Steps of RNA Transcription The sigma subunit within the polymerase recognizes the promoter sequence and a closed promoter complex is formed. The enzyme covers about 60 bp of the double helix. In the next phase, the double helix starts „melting‟ at - 10 box unwinding the DNA into single strands in the region under the core enzyme. The -10 box consistsof entirely AT pairs which have only two enzyme....
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This note was uploaded on 06/12/2011 for the course CAP 5510 taught by Professor Staff during the Spring '08 term at University of Central Florida.

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motif_finding - 4. Finding Regulatory Motifs in DNA...

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