Gene Regulation

  1. Gene Regulation
        Prokaryotic gene regulation (only in transcription)
        Constitutive genes: always needed/constantly transcribed (like mitochondria)
        Other genes only transcribed when needed
        Lac operon model
        Genes regulated @ transcription
        3 genes for lactose metabolism in E.coli on DNA (lac Y, Z, A next to each other)
        If no lactose, won’t make those enzymes but will if lactose present (RNA poly still binds to promoter though)
        E.coli prefers glucose > lactose and only metabolized lactose if not much glucose there, > energy to break down lactose
        Operon: group of genes controlled by single regulatory signal, controlled by operator
        Transcribed together; genetic structure only in prokaryotes
        Sequence of DNA with promoter, operator (switch on DNA), structural genes (protein coding seq)
        promoter/operator are binding sites on DNA that aren’t transcribed (where RNA poly attaches)
        Inducible: usually off and transcription needs to be turned on
        Repressor (protein) bound to operator; to turn on, inducer mol. Inactivates repressor
        2 ways of regulating operon
        Negative regulation: repressor prevents transcription (repressor = car brake)
        Positive regulation: transcribed a little (press on gas pedal in car)
        Negative regulation (repressor -> turns off/blocks transcription)
        If no lactose, glucose is better source of energy so lac operon is blocked/not transcribed
        If lactose present, lactose passively enters and becomes allolactose (inducer) -> binds to repressor/changes shape -> RNA poly binds to promoter/transcribes gene
        Positive regulation (activator, lactose present -> turns on transcription)
        < glucose = > transcription, > cAMP and active CAP

glucose = < transcription, < cAMP and active CAP 2 molecules facilitate transcription of lac operon cAMP = cyclic AMP Glucose inhibits production, < glucose = > cAMP, cAMP activates CAP (catabolite activator protein--helps RNA poly bind to DNA template)
Lactose present and no glucose
Lots of cAMP, cAMP activates CAP, CAP binds to promoter to stimulate transcription, RNA poly attaches fully to promoter
Lactose present and high glucose
Little cAMP, few CAP attached to promoter, RNA poly has trouble attaching to promoter -> low transcription
Eukaryotic gene regulation
Prokaryotes can only regulate proteins they produce by turning on/off transcription
Eukaryotes have many ways, no operons
Multicellular eukaryotes: regulation allows cells specialization/organize cells
Differential gene expression: expression of different genes by cells with same genome
Regulation of chromatin structure
Chromatin packaging controls gene expression
Euchromatin: loosely packed chromatin -> active genes
Heterochromatin: tightly coiled regions even during interphase like Barr body -> inactive
Nucleosomes have loose pieces/space where RNA poly can access
Modify nucleosome to regulate transcription (histone modification)
Histone methylation: < transcription Methyl groups added to N-terminus end protruding from nucleosome (AA end), hydrophobic and DNA condenses, inhibits gene expression Histone acetylation: > transcription
Regulation of transcription initiation (proteins binding to DNA)
Many mechanisms of control like aid/inhibit attachment of RNA poly and many proteins required to initiate transcription (transcription factors--interact with control elements)
General: essential for translation of proteins
Post-transcriptional regulation
introns/extrons, alternative splicing (choose between introns/extrons, different genes -> greater diversity); 5’ cap and 3’ poly A tail
Post translational regulation: folding/other chem. Modifications, modify polypeptides to get functional protein, phosphorylation