Regulation of gene expression Flashcards
What are transcription regulators + function?
Group of proteins that recognise a specific sequence of bases on the DNA (5-10bp) that are often called cis-regulatory sequences, because they are on the same chromosome as the gene they control.
The Transcription regulators bind and determine which genes are to be transcribed and at what rate.
How do transcription regulators bind?
Makes a series of contacts with the DNA, hydrogen bonds, ionic bonds and hydrophobic interactions. Often interact with structural motifs in the major groove
Why is transcription regulation simpler in bacteria?
DNA in plasmids, no histone association, no chromosomes
What is an operon? vs eukaryotes
Cluster of genes controlled by a single promoter, found mainly in bacteria. Genes in eukaryotes are often transcribed and regulated individually
Explain tryptophan regulation
Tryptophan repressor transcription regulator binds to cis-regulatory sequence, blocking the promoter, preventing RNA polymerase from binding, stopping transcription
How do transcription activators work?
Bind to poorly functioning promoter- improving the way the RNA polymerase binds.
How many transcription factors does eukaryotic RNA polymerase require to work?
5
Gene control region definition
The whole expanse of DNA involved in regulating and initiating transcription of a eukaryotic gene.
Promoter definition
Where general transcription factors and polymerases assemble
What is a cis-regulatory sequence?
Where transcription regulators bind and control the rate of assembly processes at the promoter.
What are general transcription factors + function?
Proteins that recognise specific promoters and recruit the correct RNA polymerases. Bind to core promoter upstream of gene.
Another broad class of multisubunit proteins
Coactivators and co repressors
How do they assemble on DNA?
Do not recognise specific sequences themselves however they are brought to the sequences due to transcription regulators. The appropriate combination of coactivators or co repressors and cis-regulatory sequences can crystallise the assembly of the complex on DNA
Co activator various functions
Involved in activating transcription
- bind to general transcription factors accelerating their assembly on a promotor
- form mediator complex that serves a s a bridge between DNA bound transcription activators,RNA polymerase and the general transcription factors
Another name for co-activators
enhancers
Transcription activator functions
- alter chromatin through covalent histone modifications
- nucleosome remodeling
- nucleosome removal
- histone replacement
- move from facultative heterochromatin to euchromatin, so can be assessed by general transcription factors
- promotes binding of additional regulators
- release RNA polymerase from promotors
How is RNA polymerase released from promoters?
- activator removes nucleosome block
- communicates with RNA polymerase, through coactivator, to signal it to move ahead
- activator loads elongation factors onto more DNA, allowing RNA polymerase to move onto a new promoter
Transcriptional synergy definition
Exhibited by transcription activators, where their overall transcription rate is much higher than the sub of their transcription rates alone.
6 ways transcription repressors can work
- competitive DNA binding with activators
- masking the activation surface
- direct interaction with general transcription factors
- recruitment of chromatin remodelling complexes to condense the chromatin
- recruitment of histone deacetylases
- recruit histone methyl transferase which attaches methyl groups to histones, maintaining the chromatin in the silent form
How do transcription repressors typically act?
Bring co-repressors to DNA
Insulator DNA sequence function
prevents cis regulatory sequences activating inappropriate genes. Form loops of chromatin, holding the gene and its control region in close proximity to prevent control spilling over into different genes.
Explain DNA looping
Allows a protein bound at a distance activator or repressor site to come into contact with the RNA polymerase
What is the TATA box?
Found in the core promoter region of the DNA. Binding site for TATA binding protein and other transcription factors .
Features of General Transcription Factors
- Have at least one DNA-binding domain
- Can be activated by ligand binding, phosphorylation or coactivators/corepressors
- Contain an activation domain, for regulators to bind
- bind to TATA
Examples of cis-regulatory sequences
Enhancer region, silencer region and insulator region
Difference between enhancer and promoter region
Enhancer increases the rate of transcription, promoter initiates transcription
Promoter must be close to the gene that is being transcribed whereas the enhancer does not.
Which chromatin can be added by transcription factors?
Euchromatin, loosely wrapped DNA regions containing active genes
How can chromatin be manipulated to silence transcription?
- Increase deactylation, more charges on histones, more attracted to DNA, more condensed chromatin- proteins cannot bind
- increase methylation of DNA bases cytosine and adenine, proteins cannot bind
Where is the site of epigenetic modifications on histones?
N- terminal Histone tail
Enzymes involved in methylation and acetylation
DNA methyltransferase - adds methyl groups
Demethylases- removes methyl groups
Acetyltransferases- transfer acetyl group from CoA
Histone deacetylase- removes acetyl group
