BO101 Molecular Genetics Lecture 5 Control of Gene Expression 2024 PDF

Control of Gene Expression BO101 - Molecular Genetics - Lecture 5 Dr Andrew Flaus, Biochemistry Flickr - Cut the blue wire! - brian hefele How can we regulate enzymes? ๏ Regulation of enzyme activity ‣ Feedback inhibition ‣ See Cell Biology lectures...

Control of Gene Expression BO101 - Molecular Genetics - Lecture 5 Dr Andrew Flaus, Biochemistry Flickr - Cut the blue wire! - brian hefele How can we regulate enzymes? ๏ Regulation of enzyme activity ‣ Feedback inhibition ‣ See Cell Biology lectures ๏ Regulation of enzyme production ‣ Regulation of gene expression ‣ Alter production of enzymes Campbell Biology g 18.2 fi Operons in bacteria ๏ Operon = cluster of related genes regulated by a single promoter Campbell Biology g 18.3 fi Transcription regulation case 1 ๏ Trp operon ‣ Repressor protein eg Trp repressor protein ‣ Corepressor molecule eg Tryptophan ๏ Negative gene regulation ‣ Transcription factor (TF) blocks RNA polymerase when bound to operator ‣ TF only binds operator when corepressor is present Campbell Biology g 18.3 fi Transcription regulation case 2 ๏ Lac operon ‣ Repressor protein eg Lac repressor ‣ Inducer molecule eg Allolactose ๏ Negative gene regulation ‣ Transcription factor (TF) blocks RNA polymerase when bound to operator ‣ TF only binds operator when inducer is absent Campbell Biology g 18.4 fi Transcription regulation case 3 ๏ Lac operon ‣ Activator protein eg CRP protein ‣ Coactivator molecule eg cyclic AMP (cAMP) ๏ Positive gene regulation ‣ TF activates RNA polymerase when bound to operator ‣ TF only binds operator when coactivator is present Campbell Biology g 18.5 fi Summary of transcription regulation Transcription factor binds to promoter when effector molecule … is present is absent corepressor inducer Negative regulation eg tryptophan and eg lactose and Trp repressor (case 1) Lac repressor (case 2) coactivator inhibitor Positive regulation eg cAMP and (not described in text) CAP protein (case 3) Combining transcription regulation ๏ Lac operon ‣ CAP can bind if cAMP present ‣ Lac repressor can bind if allolactose absent ‣ Competition between effects on promoter ๏ Balance of negative and positive regulation Campbell g 18.5 fi Gene regulation in eukaryotes Flickr - Colourful Singapore - swisscan Eukaryotic regulation 1. Chromatin packaging of DNA 2. Transcription Regulation not covered in BO101 ‣ RNA transcript processing not covered in ‣ Translation and post-translation BO101 Campbell Biology g 18.6 fi 1. Using chromatin for gene regulation ๏ Chromatin packaging affects accessibility TF = transcription factor accessible inaccessible ‣ Accessible to TFs and RNA polymerase if loosely packaged ‣ Inaccessible to TFs and RNA polymerase if tightly packaged Campbell Biology ed 10 g 16.22 fi 1. Using chromatin for gene regulation ๏ Chromatin packaging affects accessibility ‣ Accessible if loosely packaged ‣ Inaccessible if tightly packaged ๏ Switch by acetylation ‣ Add acetyl groups to histones proteins in nucleosome packaging Campbell Biology ed 10 g 16.22 and 18.7 fi 2. Multiple transcription factors cooperate ๏ Multiple binding sites ‣ Promotor = close to RNA pol Bound by transcription factors ‣ Enhancers = distant sites Bound by activator proteins ๏ Cooperative effects ‣ DNA can loop over to bring distant sites closer ‣ Activators and TFs can work together Campbell Biology g 18.11 fi 2. Multiple transcription factors cooperate ๏ Multiple binding sites ๏ Cooperative effects ‣ Activators and TFs can work together ๏ Switching of genes by activator combinations ‣ Rich and complex regulation is possible ‣ Switch on and off genes in different cell types Campbell Biology g 18.12 fi Misregulation of genes in cancer Flickr - thin ice warning - Dru! Oncogenes: Cancer-causing genes ๏ Oncogenes ‣ Genes that promote cancer when mutated ๏ Two types 1. Proto-oncogenes 2. Tumour suppressors Oncogenes: Cancer-causing genes ๏ Oncogenes ‣ Genes that can promote cancer if mutated 1. Proto-oncogenes ‣ Normal function is to stimulate cell growth and division ‣ Cell only expresses proto-oncogenes when needed ‣ Mutations cause proto-oncogenes to lose regulation ➔ oncogenesis 2. Tumour suppressor genes ‣ Normal function is to inhibit cell division ‣ Cell expresses tumour suppressors to prevent unneeded cell division ‣ Mutations cause loss of tumour suppression ➔ oncogenesis Cancer interferes with normal cell signalling ๏ Ras is a proto-oncogene ‣ Ras acts in signal transduction Helps switch on cell cycle when signals come from outside ‣ Ras point mutations Switch Ras ON without control Loss of control, signal stuck ON Campbell Biology g 18.24 fi Cancer interferes with normal cell signalling ๏ Ras is a proto-oncogene ๏ p53 is a tumour suppressor ‣ p53 acts in cell cycle control Switches off cell cycle when DNA is damaged “Guardian of the genome” ‣ p53 point mutations Inactivate p53 responsiveness p53 cannot halt cell cycle Cell accumulates more mutations Proto-oncogenes get mutated Campbell Biology g 18.25 fi Multi-step mutations and cancer diagnosis ๏ Mutations in several genes are needed before cell cycle control is lost ‣ Use of genomic technology to track changes ‣ Some mutants can be inherited = testing ‣ Understanding of complex molecular biology is needed Campbell Biology g 18.26 fi Summary of lecture ๏ Prokaryotes ‣ Transcriptional control Operons Repressors, activators ๏ Eukaryotes ‣ Multiple levels of control Chromatin packaging Transcription ๏ Cancer ‣ Misregulation of cell cycle control genes Learning outcomes for lecture ๏ On successful completion of this lecture, you will be able to: ‣ Explain the features of bacterial gene regulation that enable responses to environmental signals ‣ Describe how enhancers enable coordinate regulation in eukaryotes ‣ List the different levels at which eukaryotic gene regulation acts ‣ Explain how the mis-regulation of cell cycle control genes contributes to cancer