Chapter 18: Regulation of Gene Expression Flashcards
Gene regulation
Molecular components
Operator a segment of DNA that is usually positioned within the promoter or between the promoter and the coding genes that acts as the “on-off switch” for a gene
Operon- the operator, promoter, and the genes they control
Repressor binds to the operator and prevents RNA polymerase from transcribing the genes
- The repressor is the product of a separate regulatory gene with its own promoter
- Can be in an active or inactive form depending on the presence of other molecules
Corepressor- a molecule that cooperates with a repressor protein to switch an operon off
Types of negative gene regulation
A repressible operon is one that is usually on; code for repressible enzymes
- Can be inhibited when a corepressor allosterically binds to a repressor which then binds to the operator
- Generally function in anabolic pathways by suspending production of an end-product that is already in sufficient quantity
- E.g. tryptophan is a corepressor
An inducible operon is usually off; code for inducible enzymes
- Can be stimulated to turn on when a specific molecule called an inducer interacts with a different regulatory protein
- Generally function in catabolic pathways by producing enzymes only when a specific nutrient is present
- E.g. allolactose is an inducer
Positive gene regulation
A small organic molecule such as cyclic AMP (cAMP) allosteriically binds to a stimulatory protein called an activator such as CRP
The activator then binds to DNA and stimulates transcription of a gene by increasing the affinity of RNA polymerase for the promoter
Regulation of chromatin structure
Chromatin structure and gene expression can be influenced in two ways:
Chemical modification of the histone proteins of the nucleosomes
- Histone acetylation- the addition of an acetyl group to positively charged lysine in a histone tail promotes transcription by opening up chromatin structure
Chemical modification of DNA nucleotides
- DNA methylation- associated with reduced transcription in some species; can cause long-term inactivation of genes in cellular differentiation
Epigenetic inheritance
Inheritance of traits transmitted by mechanisms not involving the nucleotide sequence itself
Study of epigenetic inheritance is calle epigenetics
Control elements
Segments of non-coding DNA that serve as binding sites for proteins called transcription factors which bind to the control elements and regulate transcription
Enhancers
Distal control elements that may be thousands of nucleotides upstream or downstream of a gene or within an intron
Rate of gene expression can be strongly increased or decreased by the binding of specific transcription factors, either activators or repressors, to the control elements of enhancers
Nuclear architecture and gene expression
Loops of chromatin extend from individual chromosome territories into specific sites in the nucleus
Loops from different chromosomes may congregate at particular sites, some of which are rich in transcription factors and RNA polymerases
These may be areas specialized for a common function
Post-transcriptional regulation
Mechanisms
Allows a cell to fine-tune gene expression in several ways in response to environmental changes
RNA Processing
- Alternative RNA splicing- different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which as introns
mRNA Degradation
- Life span of mRNA molecules in the cytoplasm is a key to determining the pattern of protein synthesis
- Eukaryotic mRNA is more long lived than prokaryotic mRNA
- Nucleotide sequences that influence the lifespan of mRNA in eukaryotes reside in the untranslated region (UTR) at the 3′ end of the molecule
Protein degradation
- The length of time each protein functions is regulated by selective degradation
- Cells mark proteins for degradation by attaching ubiquitin to them
- This mark is recognized by proteasomes which recognize and degrade the proteins
Noncoding RNAs
A small fraction of the non-protein-coding DNA consists of genes for RNA such as rRNA/tRNA
A significant amount of the genome may be transcribed into noncoding RNAs (ncRNAs)
MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) are small single-stranded RNA molecules that can bind to mRNA
These can degrade mRNA or block its translation, referred to as RNA interference (RNAi)
It is estimated that expression of at least half of all human genes may be regulated by miRNAs
Cancer genes
Oncogenes are cancer-causing genes in some types of viruses
Proto-oncogenes are the corresponding normal cellular genes that are responsible for normal cell growth and division
Proto-oncogene conversion
Arises from a genetic change that leads to an increase either in the amount of the proto-oncogene’s protein product or the intrinsic activity of each protein molecule
Four main categories of changes:
- Alterations in epigenetic modifications that can lead to abnormal chromatin condensation; i.e. loosening of chromatin usually found as heterochromatin
- Proto-oncogenes are translocated to an area near an active promoter
- Amplification increases the number of copies of the proto-oncogene in the cell through repeated gene duplication
- A point mutation either in the promoter or an enhancer that controls a proto-oncogene could cause an increase in its expression
- A point mutation changes a proto-oncogene’s protein product to a more active form or one more resistanct to degredation
Tumor-suppressor genes
Normally help prevent uncontrolled cell growth by:
- Repairing damaged DNA
- Controlling cell adhesion
- Acting in cell-signaling pathways that inhibit the cell cycle
Mutations common in human cancers
- Ras proto-oncogene
- p53 gene mutation
