7. regulation of gene expression Flashcards
the two mechanisms that effect control of transcription
–binding of sequence-specific transcription factors to DNA
–control of DNA packaging and chromatin structure
how are most eukaryotic genes controlled?
complex cis acting sequences within their promoters
- recognised by TFs
- can be far away from TSS
Transciption control by transcription factors
where do they usually interact with on DNA
must recognised DNA sequences
6-8 bases
interact mainly with major grooves on DNA
contain protein features that can read DNA
often charged to bind to sequences
common DNA binding motifs of TF
–helix-turn-helix
–leucine zipper
–zinc finger
–helix-loop-helix
–homeodomain
what do TFs function as and why
dimers (homo/ hetero)
increase binding affinity and specificity
TFs can be general transcriptors or specific
How do TFs up to 100kb from transcription start site regulate transcription?
DNA looping
Do TFs always bind to DNA?
no
DNA binding TFs can recruit other regulators:
co activators/ repressors
modification of chromatin structure- interaction with histones
what do transcriptional co activators do
open chromatin structure
e.g. histone acetyltransferases. Acetylates histones
•Successive modifications open chromatin and promote transcription.
what do transcriptional co repressors do
close chromatin structure
eg. histone deacetylase
methylation: postitive charge will more likely tighten structure
what can transcription regulated activity be modulated by
external signals
Gene control functions through transcription circuits
what type of gene encodes for TFs in humans
Hox genes control brain and limb development
switch on other genes
defects can cause congenital abnormalities
what do Pax TFs control
neural crest cell migration development
p53 mutation
is a TF, activates multiple genes involved in cell cycle arrest, DNA repair and apoptosis
‘guardian of the genome’
mutated in cancers
Post-transcriptional processing – alternative splicing
E.g. calcitonin gene in humans
exon 4 and 5 cant be present at the same time
Post-transcriptional processing - RNA editing
eg. ApoB gene:
–Liver à VLDL, LDL
–Intestine à chylomicrons picks up lipid from gut and transports to liver
Post-transcriptional processing - mRNA stability
–general competition between translation and decay
–eIF2 dephosphorylation activates translation
–cytosolic mRNAs are de-adenylated, which leads to mRNA degradation
Post-transcriptional processing - mRNA stability
iron
–IRON (Fe2+) controls its own uptake
into cells
–TRANSFERRIN RECEPTOR mRNA
stability regulated by iron
Post-transcriptional processing - translational regulation with iron
–IRON (Fe2+) controls its own storage
in cells
–FERRITIN (stores iron) mRNA translation regulated
by iron
Post-transcriptional processing - miRNAs
non coding RNAs
- miRNAs (~23nt) associate to form RISC (RNA-induced silencing complex). Mixture of proteins and small RNA
- RISC then directs destruction, silencing or reduced transcription of targeted mRNA.
