BOLOGY 107 Lecture 31Outline of Last Lecture I. Gene Regulationa. Prokaryotic gene regulationb. Lac OperonOutline of Current Lecture II. Eukaryotic Gene Regulationa. Chromatinb. Eukaryotic transcription regulationc. Post-transcriptional regulationCurrent LectureEukaryotic Gene Regulationa) Conserves energyb) Responds to environmentc) Specializes cellsi) Controls both development and functiond) Growth regulationi) Mis-regulation can lead to cancere) Can occur at every step of expression2) Chromatina) DNA is in association with proteins and is highly folded and tightly packedi) Packed DNA is unavailable for transcriptionb) DNA is wrapped around histone proteins that associate into larger clustersi) Known as heterochromatin, not expressiblec) Acetylation of the histone tails prevents associationi) Known as euchromatin, DNA can be expressedii) Transcription can be regulated by which histones near which genes are disassociatediii) Heterochromatin and euchromatin tend to be clustered in different subdomains of the nucleus(1) Euchromatin in areas called transcription factories3) Eukaryotic transcriptional regulationa) More complexi) Control elements (DNA) bind to transcription factors (proteins)These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.(1) Enhancers- binding sites for activating proteins (activators)(2) Repressors- binding sites for repressing proteinsii) Transcription factors (TF)(1) General (a) Used for all genes(2) Specific (a) Only a subset of genes, tissue specific and response specific(3) Help load or block RNA polymerase(4) Contain DNA-binding and activation/repression domainsb) Action at a distancei) Most prokaryotic promoters occupy <100 base pairs, eukaryotic promoters can be >50,000 base pairs(1) Regulatory elements can be upstream or downstream, even in the coding sequence or introns(a) Proximal control elements – immediately surrounding promoter(i) Usually sites for general TFs(b) Distal control elements – away from the promoterii) Communicate via DNA bending(1) Proteins bind to DNA and assist bendingiii) Work through intermediary protein complex(1) Mediator (a) Loads polymerase, recruits enzymes to carry out chromatin modificationiv) Combinations of general and purpose-specific TFs turn genes on and off(1) Frequently see cascades – one TF stimulates the expression of another and so onc) Combinatorial codesi) Specific combinations of TFs needed for different genes in different tissues(1) Some are general or tissue specificii) Multiple activating TFs needed to recruit Mediatoriii) How do you a get tissue-specific TF to begin with?(1) TFs from the mother are not homologous within the zygote of an organism. As the zygote divides, the TFs are not distributed equally, leading to different concentrations and different genes being expressed.iv) What happens when this goes wrong(1) Tissue-specific developmental TFs expressed in the wrong place can lead to deformities(a) In one experiment, a fly had TFs moved to the head from the lower part of the body and grew legs instead of antenna on its faced) Extracellular signals can regulate transcriptioni) Signaling cascades can end with modifications to TFs(1) Mutations in pathway proteins can lead to loss of appropriate transcription control, leading to things like cancer4) Post-transcriptional regulationa) Alternative splicingi) Can also get alternative polyadelylationb) Protein stabilityi) Proteins can be targeted for destruction(1) Ubiquitination- addition of ubiquitin (marker protein)(2) Signals proteasome to destroy themc) mRNA stabilityi) Making small complementary RNA can result in mRNA being destroyed(1) Called miRNAd) Translational regulationi) Formation of localized dsRNA (or protein binding) can inhibit accessibility to ribosomese) Similar miRNA mechanism can shut down transcription by changing
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