BOLOGY 107 Lecture 31 Outline of Last Lecture I Gene Regulation a Prokaryotic gene regulation b Lac Operon Outline of Current Lecture II Eukaryotic Gene Regulation a Chromatin b Eukaryotic transcription regulation c Post transcriptional regulation Current Lecture Eukaryotic Gene Regulation a Conserves energy b Responds to environment c Specializes cells i Controls both development and function d Growth regulation i Mis regulation can lead to cancer e Can occur at every step of expression 2 Chromatin a DNA is in association with proteins and is highly folded and tightly packed i Packed DNA is unavailable for transcription b DNA is wrapped around histone proteins that associate into larger clusters i Known as heterochromatin not expressible c Acetylation of the histone tails prevents association i Known as euchromatin DNA can be expressed ii Transcription can be regulated by which histones near which genes are disassociated iii Heterochromatin and euchromatin tend to be clustered in different subdomains of the nucleus 1 Euchromatin in areas called transcription factories 3 Eukaryotic transcriptional regulation a More complex i 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 proteins ii 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 domains b Action at a distance i 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 promoter ii Communicate via DNA bending 1 Proteins bind to DNA and assist bending iii Work through intermediary protein complex 1 Mediator a Loads polymerase recruits enzymes to carry out chromatin modification iv 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 on c Combinatorial codes i Specific combinations of TFs needed for different genes in different tissues 1 Some are general or tissue specific ii Multiple activating TFs needed to recruit Mediator iii 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 face d Extracellular signals can regulate transcription i 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 cancer 4 Post transcriptional regulation a Alternative splicing i Can also get alternative polyadelylation b Protein stability i Proteins can be targeted for destruction 1 Ubiquitination addition of ubiquitin marker protein 2 Signals proteasome to destroy them c mRNA stability i Making small complementary RNA can result in mRNA being destroyed 1 Called miRNA d Translational regulation i Formation of localized dsRNA or protein binding can inhibit accessibility to ribosomes e Similar miRNA mechanism can shut down transcription by changing chromatin
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