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Introduction to Bioinformatics II
Lecture 8 By Shumaila Azam
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Transcription Factors
Transcription factors (TFs) are proteins that bind to the DNA and help to control gene expression. We call the sequences to which they bind transcription factor binding sites (TFBSs).
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Transcription factor Binding site
Transcription factor binding sites are found within larger functional units of the DNA called cis-regulatory elements. There are two main type of cis-regulatory elements: promoters, and cis-regulatory modules (sometimes called “enhancers”). TFBS transcription factor binding site (TFBS) cis-regulatory module (CRM) Image adapted from Wolpert, Principles of Development
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Control of Gene Expression: Promoters
Every gene has a promoter, the DNA sequence immediately surrounding the transcription start site. The promoter is the site where RNA polymerase and the so-called general transcription factors bind.
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Control of Gene Expression: CRMs
Additional gene regulation takes place via the cis-regulatory modules (CRMs), which can be located 5’ to, 3’ to, or within introns of a gene. CRMs can be very far away from the gene they regulate TFBS transcription factor binding site (TFBS) cis-regulatory module (CRM) click here and then select “Transcription Complex and Enhancers (586.0K)” for an animation on gene expression
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Cis-regulatory module (CRM) is a stretch of DNA, usually 100-1000 DNA base pairs in length
One cis-regulatory element can regulate several genes One gene can have several cis-regulatory modules
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Classes Enhancers Silencer Insulators
regulate gene expression positively Silencer act by silencing genes Insulators work indirectly by interacting with other nearby cis-regulatory modules
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A nutritional example: the lactase gene
© M. Halfon, 2007
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agataatgtagTccctggcctca agataatgtagCccctggcctca
A nutritional example: the lactase gene Many adult humans cannot metabolise lactose (milk sugar). A single nucleotide polymorphism (SNP), i.e., a one basepair difference in DNA sequence, correlates with activation of the lactase promoter and with lactose tolerance/intolerance. Moreover, this simple change can be seen to affect the binding activity of a transcription factor, Oct-1, to the relevant CRM. There are likely to be many such instances of how changes in gene regulation affect nutrition, health, and disease, although most remain to be discovered. agataatgtagTccctggcctca agataatgtagCccctggcctca tolerant intolerant ++ + Oct-1 binding phenotype ability to activate Olds, L. C. and E. Sibley (2003). Hum. Mol. Genet. 12(18):
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