Regulation of gene expression 1 Flashcards
Structural genes for proteins with related function are grouped together. These units are known as:
Operons
Pevents binding of RNA polymerase to promoter
Repressor
Tryptophan functions as a corepressor meaning
As the level of Trp increases within the cell this will inhibit the transcritption of the Trp operon
Benefits of regulating gene expression
Versitility and adaptation
Conservation of energy
Necessaary during development
In the eukaryotic genome:
Different cell types have different gene expression pattern
Chromatine is another level of gene regulation
Uncoupled transcription/translation
In prokaryotes, transcription is mostly regulated on the level of
initiation
What is necessary to activate the repressor?
Co-repressor
ex: Trp
What is an inducible operon?
A gene segment that is already bound by a repressor, is able to bind an inducer which releases repressor from operon
*No inducer = No expression
In the lac operon what is the inducing metabolite? Repressor?
allolactose
Glucose
*No lactose = no expression
*Lactose alone = no expression
*Requires allolactose + cAMP in order to achieve high (any) level of transcription*
For eukaryotes genes must be in what to be expressed
active chromatin
*no operons- each gene has its own promoter
In eukaryotes there is regulation at multiple levels
Chromatin: chromatin remodeling and gene rearrangement
Transcription: TFs affecting binding of RNA pol
Maturation of mRNA: processing of transcript
Translation: initiation of translation and mRNA stability
What is the definition of epigenetics?
Changes in chromatin (histones or DNA) that can be inherited.
*Note: there is no change in the nucleotide sequence
Why do we require chromatin remodeling
There will be no transcription if the promoter region is part of the nucleosome
Gene expression is also affected by their
Rearrangements
Amplification
Deletion
When a gene is actively transcribed only paternally or maternally inherited chromosome this is known as
genetic imprinting
What are the 2 most common types of posttranslational modifications of histones?
Acetylation
Methylation
Trimethylation of H3Lysine-9 attracts a a specifiv hetterochromatin called HP1 which:
Induces a spreading of Lysine-9 trimethylation followed by further HP1 binding => leading to siliencing of gene expression
Histone acetyltransferases (HATs) acetylate histone tails. Acetylation of Lys amino acids reduces net positive charge, decreases histone-DNA interaction, and creates open chomatin or euchromatin. What is the purpose of HATs?
By creating open or eu-chromatin, one can surmise that acetylated histones are indactive of active gene expression
In order to reverse the effects of HATs the active chromatin is converted into inactive chromtin via:
HDACs- histone deacetylases
What are the 3 diseases associated with genetic imprinting
Angelman syndrome: inability to express UBE3A on paternally inherited chromosome 15; Caused by mutation or deletion(>) of maternal gene; paternally imprinted gene cannot be expressed
Prader willis syndrome: results from loss of genes that are active only on paternally inherited chromosome 15 (opposite to angelman syndrome); most cases caused by deletion of a region of paternal chromosome 15; minority of cases caused by maternal uniparental disomy (UPD)–> inheritance of 2 copies of chromosome 15 from mother
Russel-silver syndrome: dwarfism caused by imprinting error; most cases (chromosome 11) result from hypomethylation of maternally expressed H19 and paternally expressed IGF2 genes; few cases (chromosome 7) have both copies of inherited from mother UDP.
What is the DNA base that accepts methyl groups resulting in posttranslational histone modification?
Cytosine
Cancer cells show a global hpomethylation of genome. Why?
Hypermethylation- can silence tumor suppressor genes
Hypomethylation- can activate proto-onco genes cMYC and H-RAS
Chromatin remodeling
A partial or complete displacement of nucleosomes from specific DNA sequences
What is the first mechanism of chromatin remodeling?
Chromatin remodeling complexes => they unwind the DNA from nucleosome and require ATP
What is the second mechanism of chromatin remodeling?
Covalent modification of histones:
HATs- create active chromatin by attaching acetyl group to Lysine residues in the tail of histones; the attachment of the acetyl group reduces the electrostatic interactions between histones and DNA
HDACs- create repressed chromatin (heterochromatin) by removing acetyl groups from histones
Lipophilic hormones regulate transcription thru
Nuclear receptors
*NRs binds DNA regulatory sequence- hormone response element; can induce or repress transcription
* Nuclear localization signal is necessary for translocation into nucleus
-Steroid hormone receptors bind either corepressor or coactivators
Activators, inducers, repressors, or nuclear receptors contain:
DNA binding domains
–>allow them to recognize and bind specific nucleotide sequences
–>DNA binding domains contaian a specific protein motif; ex: Zinc finger
Where is a common loaction for a zinc finger bindnig domain?
estrogen receptor
–> contains zinc ion coordinated with 4 cysteine residues
*Nucleotide recognition signal (NRS) binds a specific base sequence in the major groove of DNA
