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Understanding Gene Regulation: From Prokaryotes to Eukaryotes

Explore gene regulation mechanisms in bacteria and eukaryotic cells, from operons to transcriptional control and post-translational modifications. Learn how DNA packing, transcription factors, and RNA processing influence gene expression.

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Understanding Gene Regulation: From Prokaryotes to Eukaryotes

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  1. Gene Regulation

  2. Gene regulation in bacteria Cells vary amount of specific enzymes by regulating gene transcription turn genes on or turn genes off turn genes OFF exampleif bacterium has enough tryptophan then it doesn’t need to make enzymes used to build tryptophan turn genes ON exampleif bacterium encounters new sugar (energy source), like lactose, then it needs to start making enzymes used to digest lactose STOP GO

  3. Bacteria group genes together Operon genes grouped together with related functions example: all enzymes in a metabolic pathway promoter = RNA polymerase binding site single promoter controls transcription of all genes in operon transcribed as one unit & a single mRNA is made operator = DNA binding site of repressor protein

  4. So how can these genes be turned off? Repressor protein binds to DNA at operator site blocking RNA polymerase blocks transcription

  5. So how can these genes be turned off? Repressor protein binds to DNA at operator site blocking RNA polymerase blocks transcription

  6. Tryptophan operon What happens when tryptophan is present? Don’t need to make tryptophan-building enzymes Tryptophan is allosteric regulator of repressor protein

  7. Lactose operon What happens when lactose is present? Need to make lactose-digesting enzymes Lactose is allosteric regulator of repressor protein

  8. Positive Gene Regulation If glucose levels are low (along with overall energy levels), then cyclic AMP(cAMP) binds to cAMP receptor protein (CRP) which activates transcription. If glucose levels are sufficient and cAMP levels are low (lots of ATP), then the CRP protein has an inactive shape and cannot bind upstream of the lac promotor.

  9. Control of Eukaryotic Genes 2007-2008

  10. Points of control The control of gene expression can occur at any step in the pathway from gene to functional protein 1. packing/unpacking DNA 2. transcription 3. mRNA processing 4. mRNA transport 5. translation 6. protein processing 7. protein degradation

  11. 1. DNA packing as gene control Degree of packing of DNA regulates transcription tightly wrapped around histones no transcription genes turned off • heterochromatin darker DNA (H) = tightly packed • euchromatin lighter DNA (E) = loosely packed H E

  12. DNA methylation Methylation of DNA blocks transcription factors no transcription  genes turned off attachment of methyl groups (–CH3) to cytosine C = cytosine nearly permanent inactivation of genes ex. inactivated mammalian X chromosome = Barr body

  13. 2. Transcription initiation Control regions on DNA promoter nearby control sequence on DNA binding of RNA polymerase & transcription factors “base” rate of transcription enhancer distant control sequences on DNA binding of activator proteins “enhanced” rate (high level) of transcription

  14. Model for Enhancer action Enhancer DNA sequences distant control sequences Activator proteins bind to enhancer sequence & stimulates transcription Silencer proteins bind to enhancer sequence & block gene transcription Turning on Gene movie

  15. Transcription complex Activator Proteins • regulatory proteins bind to DNA at distant enhancer sites • increase the rate of transcription Enhancer Sites regulatory sites on DNA distant from gene Enhancer Activator Activator Activator Coactivator E F B RNA polymerase II H TFIID A Coding region T A T A Core promoter and initiation complex Initiation Complex at Promoter Site binding site of RNA polymerase

  16. 3. Post-transcriptional control Alternative RNA splicing variable processing of exons creates a family of proteins

  17. 6-7. Protein processing & degradation Protein processing folding, cleaving, adding sugar groups, targeting for transport Protein degradation ubiquitin tagging proteasome degradation Protein processing movie

  18. Gene Regulation 7 6 protein processing & degradation 1 & 2. transcription - DNA packing - transcription factors 3 & 4. post-transcription - mRNA processing - splicing - 5’ cap & poly-A tail - breakdown by siRNA 5. translation - block start of translation 6 & 7. post-translation - protein processing - protein degradation 5 4 initiation of translation mRNAprocessing 2 1 initiation of transcription mRNA protection 4 mRNA splicing 3

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