Control of Gene expression Flashcards
Constitutively expressed genes
Reads obtained from different cells are similar indicating that this gene is expressed at a similar level in different cell types
How can we visualise which genes are expressed in a cell?
Through RNA sequencing: number of reads is proportional to the expression level of a gene
Why is there a higher number of reads for exons than introns?
Because introns are usually degraded by nucleases when transcribed
When is a homogenous signal seen between exons and introns?
in non-mature RNA
Tissue-specific genes
genes expressed only in a specific cell type
Enhancer
Control the transcription output of the gene
Location of the promoter
Upstream of the transcription unit: localised in proximity of the transcription start site
Transcription unit
exons+ introns
Transcription start site
where RNA polymerase binds to transcribe the gene
Types of cis-regulatory sequences
- Enhancers
- Silencers
Cis-regulatory sequences
Regulate the expression of a gene located on the same DNA
Trans-regulatory sequences
Regulate the expression of genes located on another chromosome
Composition of Transcription regulators
DNA-binding domains
Effector domains
DNA-binding domains
recognise specific DNA sequences and sites
Effector domains
involved in the regulation of genes: tell a protein where to bind and what to do
What can effector domains do?
modify chromatin by depositing acetylations, methylations
What can transcription regulators recognise?
The outside of the DNA double helix which the edge of each bp presents a distinctive aptter of hydrogen-bond donors and acceptors and hydrophobic patches
How can we monitor interaction between TF and DNA?
Using antibodies: Chromatin Immunoprecipitation sequencing ChIP-Seq
What is the interaction between TF and DNA?
Highly specific
Which is the most difficult attachment for DNA-binding proteins?
distinguishing between C-G and G-C in minor grooves
Which are the main signals that control transcription factors?
- Protein synthesis
- Ligand binding
- Covalent modifications [methylation, acetylation]
- Addition of an additional subunit
- Association with an inhibitor
- Stimulation of nuclear entry
- Release from membrane
Ligand bind
Activates TF when a ligand binds to a TF such as glucocorticoid
Association with an inhibitor
TF is bound to an inhibitor which when phosphorylated is removed in order to activate the TF
How do right enhancers express a gene at the right time?
Because of the presence of DNA loops
DNA loops
Takes the enhancers near the gene when needed, making the gene express certain features
What helps make DNA loops?
Cohesin
Insulator elements
Separate one transcription unit form the next
Where do a significant proportion of mutations take place?
In enhancers
What do insulator elements prevent?
Prevent transcription regulators from influencing distant gene and they compartmentalise a given regulatory domain by forming loops
Superenhancers
A complex of several enhancers: carry out the work of multiple enhancers; has many more binding sites for TR
What are superenhancers found to be associated with?
Cancer genes; they make a cell more susceptible to the presence of drugs
