Transcript Gene_expression

Gene Regulation
Regulation of gene expression
•
refers to the cellular control of
the amount and timing of
changes to the appearance of
the functional product of a gene.
Basically, anything that can
regulate for example
•
–
–
–
–
Chemical and structural
modification of DNA or chromatin
Transcription
Post-transcriptional modification
mRNA degradation
Modification of DNA
• Chemical
– Methylation of DNA by DNA
methyltransferases
– gene silencing
– Able to maintain the gene in
an inactive state
– Very much eukaryotic event
– Example: arabidopsis
thaliana dna methylation
Modification of DNA
• Structural
– Histone acetylation.
– Histone
acetyltransferase
enzymes (HATs)
– Histone Deacetylases
(HDACs)
– dissociate the DNA
from the histone
complex, allowing
transcription to
proceed.
Regulation of transcription
• Regulation of transcription controls when
transcription occurs and how much RNA is
created. Transcription of a gene by RNA
polymerase can be regulated by at least five
mechanisms:
1. Specificity factors
2. Repressors
3. General transcription factors
4. Activators
5. Enhancers
Specificity factors
1. alter the specificity of RNA polymerase for a given
promoter or set of promoters, making it more or
less likely to bind to them
2. Example: Glucocorticoid receptor
Repressor
1. bind to operator
2. impeding RNA polymerase's progress along the strand,
thus impeding the expression of the gene.
3. coded for by regulator genes
General transcription factor
• protein transcription
factors that have been
shown to be important in
the transcription of genes
to mRNA templates.
Activators
•
•
DNA-binding
protein that
regulates one or
more genes by
increasing the rate
of transcription.
Coactivators
1. Interact with basal
transcription
machinery
2. Act on chromatin
bound to histones
Enhancers
• Distant DNA elements
• Multiple binding sites for sequence specific
transcriptional activators
Translational Control
• mRNA localisation
• mRNA translation
• mRNA stability
Cytoplasmic localisation of mRNA
• Microtubules and motor proteins transport mRNA
• Microfilaments anchor mRNA
mRNA Translation
• Mechanisms exist to alter rate of translation
mRNA stability
1. Capping
2. Splicing.
3. Addition of poly(A) tail
Splicing
• removes the introns, noncoding regions
that are transcribed into RNA, in order to
make the mRNA able to create proteins.
• Cells do this by spliceosome's binding on
either side of an intron, looping the intron
into a circle and then cleaving it off.
• The two ends of the exons are then joined
together
Post-translational Control
• Proteasomes
– Degradation of cellular protein that have been
marked for destruction
– Ubiquitination
– Done by ubiquitin ligases