lect 19: control of gene expression Flashcards
what are the learning objectives of this lecture?
-describe the components and control mechanisms of operons in prokaryotic cells
-describe the four levels of regulation of gene expression in eukaryotic cells
-explain how the nuclear pore complex regulates movement of materials
what is the differences between a transcription regulator and a transcription factor?
-transcription regulator= any molecule that influences transcription of a gene
-transcription factor=a protein that influences transcription of a gene
can be:
-repressors=turn genes off
-activators= turn genes on
what is gene regulation in bacteria?
-circular, double-stranded
-nearly all DNA encodes RNAs or proteins
Operons: allows bacteria to control transcription of genes in a group
genes involved in same biological process often grouped=operons
-coordinated regulation of entire group
-start/stop of transcription/translation precisely regulated
-unlike euks: which individually transcribe genes which makes it more complex
what does the operon consist of and what does it create?
what are the two examples of bacterial operon?
Trp operon (repressible operon)
-active when corepressor is bound
-bound=repressing transcription
lac operon (inducible operon)
-active when lactose is not bound
-when bound=induce transcription
what is the Trp operon?
A-E involved in tryptophan synthesis
-if decreased trp=increase transcription of Trp operon
-repressor won’t bind if not alot of trp due to lack of corepressors (can’t bind to operator) which means nothing is blocking transcription
-so we can transcribe to make trp
-active state=trp bound
what is Lac operon?
lactose need proteins/enzymes to breakdown
when repressor doesn’t have lactose bound to it, it is now in its active state
-we want to increase transcription of a, y, z (enzymes that breakdown lactose)
-lactose binds=inactive form (wont bind to operator)
what is the overview of gene regulation in eukaryotes?
-more than 200 cell types with different functions (each cell has same genome so only differentiate in regulation of gene expression)
-between 20,000 and 25,000 genes
what are the levels of gene expression in eukaryotes?
-genes turned on/off by regulatory proteins
-each cell type has same DNA but unique set of proteins
four levels of gene expression:
1. transcriptional control: in nucleus, whether transcription happens
2. processing control: in nucleus, mods at pre-mRNA
3. translational control: in cytoplasm, whether translation happens
4. posttranslational control: in cytoplasm
what is the overview of transcriptional control?
-differential transcription
-transcription regulators (enhancers)
-regulation of chromatin structure (chromatin remodeling complex, histone modification)
-paused polymerase
-transcriptional repression (deacetylation, DNA methylation, long noncoding RNAs)
what is transcriptional control using differential transcription?
-regulation of which genes are transcribed into RNA
differential gene expression (not always fixed if on or off)
-cells at different stages of embryonic development
-cells in different tissues
-cells exposed to different types of stimuli (environmental)
what is transcriptional control using transcription regulators?
what is the example of transcription activators?
-DNA elements that increase transcription rate
characteristics
-usually located far away
-upstream or downstream
-may be inverted but still functional (different than promoters)
how do enhancers work when they are so far away?
how does a location far from the gene influence its transcription?
-“looping” of DNA brings promoter and enhancer into close approximation
-often involves additional proteins to close loop (e.g. protein complex called Mediator (in purple))
what is the regulation of chromatin structure?
changes in nucleosomes allow access to DNA
-chromatin remodeling complexes
-histone-modifying enzymes
what are the chromatin remodeling complexes?
-large, multi-protein complexes
-ATP-dependent
change position of nucleosome
-DNA more accessible
-DNA less accessible
what are the ways in which the chromatin-remodeling complex works?
mobilize/restructure nucleosomes
-thought to disrupt histone-DNA interactions
what are histone-modifying enzymes in regulation of chromatin structure?
-covalent modification of core histone protein tails
-addition/removal of acetyl, methyl, phosphate groups
modifications affect chromatin packing
-e.g. acetylation of lysine decrease tail affinity for neighbouring nucleosomes which causes loosening of chromatin structure
what is the graph of transcriptional activators and chromatin-remodeling proteins?
what is the transcriptional activation from paused polymerase?
-RNA polymerases are also bound to the promoters of many genes that show no evidence they are being transcribed
-the polymerase may initiate transcription but may be paused at the elongation stage of transcription
-RNA polymerases situated downstream of promoters may be held in the paused state by bound inhibitory factors
-the induced release of paused polymerases may facilitate the rapid activation of genes in response to developmental or environmental signals
what is deacetylation in transcriptional repression?
histone deacetylases (HDACs)
-remove acetyl groups=repress transcription (gene silencing)
-HDACs are subunits of larger complexes or corepressors
-recruited to specific gene loci by transcription factors
what is DNA methylation in transcriptional repression?
DNA methyltransferases
-methylate C5 of cytosine
-methylation patterns of gene regulatory regions change during cellular differentiation
-activity of certain genes varies according to changes in DNA methylation
what are long noncoding RNAs (lncRNAs) in transcriptional repression?
-LncRNAs: 200 nucleotides long
-most associated with gene repression
-E.g. Xist which is important in X chromosome inactivation
what is processing control?
in nucleus, what happens to pre-mRNA strand
-alternative splicing
-sequence-specific nucleus export
