regulation and gene expression Flashcards
how is the expression of most genes regulated
-most genes are expressed at different levels therefore needs regulation
-Microorganisms adapt their profile of expressed genes to utilize available nutrients.
-The diversity of cell type in multicellular organisms reflects different protein profiles that are dependent upon distinct transcript patterns.
-Cell differentiation and development programmes are driven by changes in gene expression.
-House-keeping genes are constitutively expressed- consistently expressed
-The expression of regulated genes can be induced/activated or repressed
-unregulated gene expression can lead to uncontrolled growth of cells
what happens with Protein interactions with specific DNA and RNA sequences
-A key underlying principle of regulated gene expression is the sequence-specific binding of proteins to regulatory elements (sequences) within DNA or RNA.
-A mutation affecting the regulated expression of a gene can be in cis (within the same gene) or in trans (in a different gene).
-cis mutations identify DNA/RNA sequences that affect gene regulation.
-trans mutations identify (protein or RNA) factors that regulate the expression of a target gene.
what are most genes regulated at
-transcription level- where gene is activated, transcriptional level of gene is increased
-Transcriptional regulation is the primary level of control for most genes.
-Transcriptional regulation limits wasteful production of unrequired biomolecules
-RNA transcribed by RNA polymerase
what are the two different types of effects on transcription can transcription factors have
-can either activate or repress
-protein factors regulate expression of genes- increase or decrease
-Transcription factors can act to up- or downregulate expression.
-Factors that cause activation are known as trans-acting activators. Upregulated genes are under positive control.
-Factors that cause downregulation are known as trans-acting repressors. -Downregulated genes are under negative control.
-Activators promote expression at weak promoters.
-Activators in E. coli interact with the a-subunit of RNA polymerase and promote DNA binding.
how can transcription factor activity be modulated
-The activity of transcriptional activators and repressors can be regulated through interaction with other molecules. These molecules can stimulate or inhibit activity of the transcription factor.
-Inducers( e.g. small hormone molecules) binds to transcription factors. They stimulate activators or inhibit repressors.
-Corepressors (e.g. small molecules, leads to repression of transcription) bind to a transcription factors. They stimulate repressors or inhibit activators.
-Genes under positive or negative control can be induced and/or repressed.
what’s lacI repression of the lac Operon
-lac operon is the model if gene regulation
-The lac operon encodes three genes associated with lactose metabolism: lacZ, lacY and lacA.
-Expression of the lac operon is controlled by the transcription repressor gene, lacI.
-The lac repressor binds to lacO operator sequences and blocks RNAP activity.
-DNA binding activity of the lac repressor is inhibited by inducer molecules such as lactose
-lacZ- translated into beta- galactosidase
-lacY- translated into lactose permease
-lacA- translated into galactoside acetyltransferase
what’s happens with CAP activation of the lac Operon
-The lac operon is also regulated by a transcriptional activator called catabolite activator protein (CAP)- stimulate transcription
-CAP binds to the lac promoter when associated with the inducer cyclic AMP and stimulates transcription.
-cAMP production is inhibited in the presence of glucose (a preferred carbon source)- cAMP has structural variation as there can be the phosphate on 5’ and also on the 3’
-The lac operon is expressed only in the absence of glucose and presence of lactose- controlled by glucose availablility, only cAMP binds in absence
-Lac expression is inducible and under both positive and negative control.
how can Gene expression be regulated in eukaryotes at the level of RNA processing
-Pre-mRNA splicing can occur in different patterns.
-This can lead to the production of two distinct proteins from the same pre-mRNA.
-Alternatively, there might be a nonproductive pathway, in which the mRNA is degraded
-pattern of splicing can be variable- alternative pre-splicing Sio different splicing sites are recognised, and the same pre-mRNA transcript spliced in different ways
what’s Translation level control of gene expression
-Gene expression can be regulated at the level of translation.
-Translation is normally regulated at the initiation step.
-Translation can be regulated at a global level, for all transcripts. Translation is downregulated in eukaryotic cells as part of the integrated stress response (ISR).
-Translation can also be regulated by transcript-specific mechanisms. -Expression of the mRNA encoding the iron-binding protein ferritin is responsive to cellular Fe2+ levels- needs high concentration for production of ferritin
-cells can shut down production of proteins due to stress response pathways
how does Translation inhibition by phosphorylation of eIF2a occur
-During translation initiation, eIF2 hydrolyses GTP to GDP.
-Regeneration of the eIF2/GTP complex requires the initiation factor eIF2B.
-The ISR leads to the phosphorylation and inactivation of the a subunit of eIF2
-Phosphorylated eIF2a binds very tightly to eIF2B and is trapped in a complex that cannot be recycled.
what can protein function be regulated by
-post-translational modifications
-Many proteins are processed or post-translationally modified.
-Phosphorylation of serine, threonine or tyrosine residues is the most common form of post-translational modification.
-Phosphorylation often affects a protein’s ability to interact with other molecules.
-Phosphorylation is readily reversible. Phosphorylation is driven by protein kinases and reversed by phosphatases
