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GENE REGULATION ch 18 CH18 Bicoid is a protein that is involved in determining the formation of the head and thorax of Drosophila.
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I. Overview of gene regulation
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Both prokaryotes and eukaryotes regulate gene expression in response to environmental conditions
They only make those proteins that they need to function, often only making those proteins at specific times This was favored by natural selection. Since all organisms do this, it evolved early In multicelled eukaryotes this also regulates development and is responsible for creating the different cell types
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II. Gene regulation in Prokaryotes
A. General characteristics of prokaryotic gene regulation: the operon
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Operon: cluster of functionally related gees under the control of a single on/off switch: the operator An operon contains the promotor, the operator, and all the genes under their control The operator binds repressor proteins that stop transcription by preventing RNA polymerase from binding to the promoter
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Some operons are repressible operons: they are usually on and repressor turns them off (trp operon)
Some operons are inducible operons: they are off and inducer turns them on (lac operon) Inducible operons are part of catabolic pathways while repressible operons are part of anabolic pathways
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B. The lac operon (an inducible operon)
Involved in the breakdown of lactose for energy when no glucose is around In order for the lac operon to be on: Cap protein must bind to activator site Glucose prevents CAP from binding Repressor must be off of the operator
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C. Trp operon (a repressible operon)
Involved in the production of tryptophan, an amino acid Trp operon is on UNLESS there is excess tryptophan
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III. Eukaryotic gene regulation
Multicelled eukaryotes are more complex than prokaryotes so gene regulation occurs at many levels Gene regulation is designed to: Maintain homeostasis promote cell specialization thru differential gene expression
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A. Regulation of Chromatin structure
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Heterochromatin is tightly packed thus genes can’t be transcribed
Acetylation of histones loosens the heterochromatin allowing it to be transcribed Methylation condenses the DNA preventing it from being transcribed which may play role in gene inactivation during differentiation Sometimes these chemical modifications of DNA can be passed on to offspring. This is called epigenetics
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B. Transcriptional control in Eukaryotes
1. Structure of a typical eukaryotic gene Upstream control elements: regulate transcription initiation by binding transcription factors Promoter: starts transcription Coding sequence: in between promoter and termination sequence
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2. role of transcription factors
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general transcription factors allow transcription to occur
activators are transcription factors that bind to enhancers upstream and induce transcription repressors are transcription factors than bind to silencers upstream and inhibit transcription
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C. Post-transcriptional control
Allows cell to fine tune gene expression quickly in response to environmental changes
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1. Alternate gene splicing
Production of different mRNAs from the same primary transcript depending on which exons are spliced together
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2. Rate of mRNA degradation
There are sequences in 3’end of mRNA that regulate its lifespan The quicker the mRNA is degraded, the less protein made
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3. Initiation of translation
Regulatory molecules can bind to mRNA that block initiation of translation
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4. Protein processing and degradation
If a protein is degraded it can’t be used
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5. RNA interference Parts of the genome don’t code for proteins but produce other types of RNA RNA interference is the inhibition of gene expression by these RNAs Small interfering RNAs (siRNA) bind to mRNA to induce its degradation
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IV. Differential gene expression and development in multicelled eukaryotes
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Fertilized egg divides by mitosis to produce all cells in multicelled eukaryotes
Cell division produces identical cells Cell differentiation produces specialized cells thru differential gene expression Morphogenesis results in shaping of organism
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All three events are based on processes that occur at the cellular level
Since transcriptional activators stimulate transcription, then different cells must have different sets of transcriptional activators
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Different cells express different sets of genes
What “tells” a cell which genes to express?
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A. Cytoplasmic Determinants and Induction 1. Cytoplasmic Determinants
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proteins, mRNAs, and organelles aren’t distributed evenly in a fertilized egg cell
many of these proteins and mRNAs are cytoplasmic determinants that influence the fate of the cells when cell divides, determinants are not equally distributed therefore, nuclei in each cell are exposed to different determinants. This helps direct what genes are expressed during cell differentiation
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2. Induction As the number of cells increases, different embryonic cells secrete signal molecules that affect gene expression in neighboring cells thru the cell signaling pathway This results in changes in gene expression
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Induction and cytoplasmic determinants lead to formation of 3 germ cell layers and ultimately all of the specialized cells in organs and tissues
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Once induction occurs and certain cells start expressing different genes, those cells are determined to become a specific cell type The expression of these specific genes leads to expression of other genes resulting in cell differentiation
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IV. Gene regulation and Cancer
A. Cell Cycle control Control of cell cycle is like accelerator and break When new cells are needed, accelerator is used When new cells not needed brake is used
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B. Proto-oncogenes
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Are normal proteins that stimulate progression thru the cell cycle
Many are intracellular cell signaling molecules involved in activating transcription Mutations cause proto-oncogenes to become oncogenes Results in overstimulation of cell division
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Ex: Ras proto-oncogene
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Normal ras is activated by binding of growth factor to its receptor
This activated ras activates a series of protein kinases that activate a transcription factor which induces transcription of cell cycle stimulatory protein Mutated ras does not need growth factor activation
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C. Tumor Suppressor genes
Normal tumor suppressor genes inhibit cell division Some repair DNA Some involved in anchorage dependence Some are part of cell signaling pathway that inhibit cell division
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Ex: p53 DNA damage activates p53 which induces transcription of a protein that inhibits cell cycle Mutation in p53 fails to induce transcription of this protein
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