Lecture 25. Regulation of Gene Expression Flashcards
What is the function of gene expression ?
Required to convert the information that resides within our DNA into gene products
What do gene products of gene expression influence ?
The phenotype of the cell
What are the gene products of gene expression ?
RNA and protein
How do cells differentially express their genes ?
They turn on or off specific subsets of genes at different times and places
What is the function of differential expression ?
To achieve huge diversity of cell types or cellular activation states
What are some cellular activation state ?
Dividing, non-dividing, differentiating, activated, secreting
What does the ability to regulate gene expression occur through ?
Molecules that bind to the regions that flank the coding sequences of genes
What is the ability to regulate gene expression critical to achieving ?
Different outputs/phenotypes from the same genome
What is the classical definition of a gene ?
A genetic variant affecting a trait where a genetic mutation has an effect on some phenotype
What are the two locations of mutations ?
- Protein coding part
2. Regulatory part
What is the molecular definition of a gene ?
A transcriptional unit encoding an RNA or protein, where the gene product has some biochemical or cellular function
What does the gene encompass ?
- The coding sequence
2. DNA regulatory elements
What is the coding sequence ?
The sequence that is transcribed into RNA
What is another name for DNA regulatory element ?
Promoter
What is the function of DNA regulatory elements ?
Regulate the expression of the gene in a positive or negative manner
What can variants of a gene be caused by ?
- Mutation
2. Natural sequence variation
What areas do variants of a gene effect ?
Either:
- The coding sequence
- Regulatory sequence
What do changes to gene expression effect ?
When, where and how much of a gene is expressed which in turn effects phenotypes
What do changes to the coding sequence of the gene effect ?
They subtly or radically change the protein or RNA product encoded by the gene and also impacts the cellular phenotype
What do all genes encode ?
RNA molecules
Which RNA molecules are translated into proteins ?
mRNA
What makes cells different from each other and responsible for the different activity states?
The protein coding fraction of the genome
Do all genes that encode RNAs become translated into proteins ?
No
What do RNAs which do not become translated into proteins possess ?
Enzymatic or regulatory functions
What are the key non-translated RNAs ?
- Ribosomal RNA
- Transfer RNA
- Regulatory RNA
What are some types of regulatory RNAs ?
- snRNA (Small nuclear RNA)
- microRNA (miRNA)
- Long non-coding RNA (lncRNA)
What are the major gene expression products ?
- Proteins
- Structural RNAs
- Regulatory RNA
What are the structural RNAs ?
- rRNA
2. tRNA
How much do ribosomal and transfer RNAs comprise of the total RNA within cells ?
80-90%
How much of the total RNA within the cell does mRNA comprise of ?
2-3%
What are some characteristics of prokaryotic genomes ?
- Relatively compact
2. Gene dense
What do genomes of higher organisms contain ?
A huge proportion of non-coding sequences
What does the non-coding sequence have ?
Gene regulatory function
How many protein coding genes is there in the human genome ?
25000
What does non-coding sequences do ?
Regulate the expression of the coding fraction of the genome
How do higher eukaryotes get more from their genes ?
Alternative splicing of their protein coding mRNAs
What does alternative splicing of the protein coding genes of mRNAs achieve ?
Make different variations of the same protein or proteins with very distinct functions
What are fully differentiated cells capable of ?
Expressing all of the genes required to build an organism
Where do all cells differentiate from ?
A fertilized embryo
What happens as cells differentiate ?
They lose expression of some genes and acquire expression of others
In general, most cells are capable of reconstituting the whole organism upon reaching the fully differentiated state. What are the exceptions to the rule ?
- Where cells lose their nuclei as they differentiate eg. erythrocytes
- Where their genome is irreversibly altered in some way eg. senescent cells that have lost their chromosome ends called telomeres (skin cells or neurons)
What switches on or off the expression of specific genes that distinguish one cell type from another?
Environmental and developmental cues through activating transcription factors
Are all genes expressed in every cell ?
No
What is differential gene expression controlled through ?
Activating signaling pathways that activate transcription factors
How are transcription factors switched on ?
Achieved through external signals from the environment or other cells
What are spatial signals ?
Instruct cells within the embryo to express genes involved in making the different parts of the fly along the anterior to posterior axis and instructing what is the dorsal or ventral surface
What is bicoid ?
- A transcription factor that forms a gradient running from head to tail of the developing embryo
- The gradient then induces the expression of a variety of transcription factors depending on the bicoid concentration
What are some transcription factors ?
- Hunchback
- Kruppel
- Knirps
- Giant
What does the different combination of transcription factors do ?
Switched on a battery of additional developmental genes that tell the cell where they are and what what fly parts they should specify
What specifies where the cells are and what fly part they should specify ?
Hox genes
What do hox genes do ?
Switch on the correct genes to make a leg, a wing, an antenna, a sex bristle etc
What are pathogen associated molecular patterns ?
Receptors for conserved components of infectious agents
What is the function of pathogen associated molecular patterns receptors ?
Enable cells of the immune system to detect the presence of pathogens
What is a class of pathogen associated molecular patterns receptors ?
Toll-like receptors
What is the function of a toll-like receptor ?
Detects foreign substances
What does the binding of a PAMP receptor to a toll-like receptor activate ?
A transcription factor called NFkappaB
What does NFkappaB do ?
Involved in coordinating the process of inflammation, which helps the body fight infection