BIOL 218: Chapter 8
43 Cards in this Set
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Housekeeping proteins
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•common to all cells (RNA polymerases, ribosomal proteins, metabolic proteins, repair proteins, cytoskeletal proteins)
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Points at which gene expression is regulated
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1.When a given gene is transcribed and how often
2.How RNA transcript is spliced or processed
3.Selecting which mRNAs are exported into the cytosol
4.Selectively degrade certain mRNA molecules
5.Selecting which mRNAs are translated by ribosomes
6.Selectively activating or inactivatin…
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Order of events leading to Eukaryotic transcription
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•Chromatin remodeling, activator proteins, general transcription factors and RNA polymerase II work together to turn gene expression on and off
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The promoter
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•is the DNA sequence (surrounding the TATA box) where the
general transcription factors and RNA polymerase II assemble
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The regulatory sequences
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•(elements) serve as binding sites for gene
regulatory proteins whose presence on the DNA affect the rate of transcription initiation
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Regulatory sequences can be located
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•adjacent to the promoter, far
upstream of it, or even within introns or downstream of the gene
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Transcriptional regulators (Transcription Factors
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•proteins which recognize regulatory DNA sequences
- Bind to DNA and effect the rate of transcription (either stop or speed up!)
•Allow “fine tuning” gene expression
•Bacteria have several 100, human several 1,000!!
•Regulators bind VERY specifically into a defined shape via h-bo…
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Regulator DNA sequences
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•areas on the DNA recognized by regulatory factors
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Activator
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•a protein that binds to a specific regulatory region of DNA to activates (turn on!) transcription of an adjacent gene
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Repressor
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•a protein that binds to a specific regulatory region of DNA to repress (turn off!) transcription of an adjacent gene
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Repressors and Activators
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•Can work upstream or downstream from the promoter
•Can work from thousands of nucleotides away from promoter
–How does this work?
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On-off switch of transcription is
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dynamic
and involves activators, repressors and
chromatin remodeling
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TURNING GENES ON!
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-Chromatin must be opened
-Activators must bind
-General transcription factors must bind
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Activators
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Activators can be “constitutive” or activated by second messengers (see chapter 16 for example of second messengers)
The activity of activators can be altered by phosphorylation (turned on or off)
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Activator protein binding....
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triggers formation of the pre-initiation complex
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In eukaryotes, gene activation occurs at...
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a distance
-activator proteins can enhance transcription even when they are 1,000s of base pairs away!
-activator proteins can be bound upstream or downstream from the gene!
-mediator: between activator and transcription complex
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Many activators need to...
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bind to the promoter
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Tissue-specific activators or transcription factors
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•interact with more
ubiquitous activators expressed in every cell
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Hydrophobic hormones can...
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regulate transcription directly
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TURNING GENES OFF!
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-Chromatin must be tight/condensed
-repressors prohibit GTFs binding
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Repressors block
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binding of RNA polymerase
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Some repressors are
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“constitutive” or “always active”
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The activity of repressors
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can be altered by phosphorylation (turned on or off)
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Gene expression can be controlled....
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in response to the cells metabolic needs!
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in response to the cells metabolic needs!
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attach acetyl group to lysines “opens DNA”
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Histone Deacetylases (HDACs)
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remove acetyl group from lysines decrease accessibility “closed DNA
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A single transcription regulator is able to...
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•switch whole groups of genes on or off,
•As long as different genes contain the DNA sequence for the transcription factor
–Both activators and repressors
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Combinatorial Control
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•Typical gene controlled by dozens of transcription regulators
–Both repressors and activators
–Help determine the final level of expression for a gene
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Combinatorial control
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•groups of regulatory proteins work together to determine the final rate of transcription initiation
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Combinatorial control can
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create different cell types
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how does a cell remember which genes it needs to turn on and when?
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1.Positive feedback loop
–Key transcriptional regulator activates transcription of own gene
2.Propagation of condensed chromatin structure from parent to daughter cell (epigenetics are heritable!)
3. DNA methylation patterns (also heritable)
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Positive feedback loop
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–Key transcriptional regulator activates transcription of own gene
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Maintenance methyltransferase
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guarantees that once has pattern of methylation has been established, it is inherited by progeny DNA
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Formation of an entire organ
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can be triggered by a single transcription factor
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Post-transcriptional controls
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Alternative splicing
UTR regions – shape of UTR effects binding of activators/repressors
Small regulatory RNAs – cause degradation of mRNA
Protein degradation – the proteosome
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DICER
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•nuclease that cleaves the double-stranded RNA into shorter fragments
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RNA interference (RNAi)
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•Degrade foreign RNA molecules
– double-stranded RNA
•Attract DICER - nuclease that cleaves the double-stranded RNA into shorter fragments
–Small interfering RNAs – siRNAs
•Incorporated into RISCs (RNA-induced silencing complex) - discards one strand of siRNA and uses remaining to loc…
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Proteolysis
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process where enzymes break proteins down into their constituent amino acids
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Enzymes = Protease
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hydrolyze the peptide bonds between amino
acids
1.Rapidly degrade proteins with short lifetimes
2.Eliminate misfolded or damaged proteins
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Stoppers
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bind the proteins to be digested
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Proteasomes
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- location where most proteins are broken down
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Proteins are marked for degradation by
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covalent addition of ubiquitin
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Protein production requires many
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steps; each step can be controlled to maintain perfect function
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