5. Regulation of gene expression Flashcards
What is gene expression
is the translation of the genetic information into functional molecular proteins or biologically acctive RNAs
At what points can gene expression be regulated
- transcriptional control
- RNA processing control
- RNA transport and localization control
- translation control
- mRNA degradation control
- protein activity control
When does bacterial gene regulation primarily occur
transcription initiation
How can one specific sigma factor regulate an entire group of genes
when they share the same/similar -10/-35 sequences
How are functionally related bacterial genes often arranged
in operons
Example:
- 5 genes that participate in the synthesis of the amino acid tryptophan are transcribed as a poly cistronic mRNA from a single promoter
- whether initiation occurs is dependent on operator
How does the tryptophan operator work?
- if free tryptophan level are high, tryptophan binds a transcriptional repressor protein
- represses interation with operator and blocks trancriptional initiation
- if low tryptophan level
- represser unable to interact with operator
- genes are transcriped to synthesize more
How are lac and tryptophan operons different
- Lac operon: ligand binds to remove regulatory protein from DNA this switches the gene on
- Tryptophan: ligand binds to allow regularory protein to bind to DNA switches. gene on
What do transcription factors do?
bind to regulatory DNA sequence to activate or repress transcription initiation
- bind to major groove of DNA forming H bonds between amino acid and bases
Only when will a gene be regulated by a particular TF
if the correct DNA sequence is found in its gene control region
What is a helix turn helix DNA binding domain
- red COOH end binds in major groove of DNA by series of hydrogen bonds. Amino acids defines the DNA sequence binding specificity
- the blue acts to stabilise the bound protein DNA complex
What is a Homeodomain
helix turn helix motif and consists of 3 alpha helix bundle with alpha recognition helix binding in the major groove
- exclusively eukaryotic
What are TF genes with homeobox called
hox
What is the zinc finger binding domain
compromises two antiparallel beta strands and one alpha helix forming a ‘finger-like’ projection that binds DNA
- example cysteine and histidine coordinate a zinc ion
how do multiple ZnF motifs within a TFs DNA binding domain help
combination gives extra specificity to which DNA sequence the TF interacts with
What are the principle dimerization domains
- leucine zipper
- helix-loop-helix (HLH)
What does the basic leucine zipper do
conserved hydrophobic leucine residues line one surface of the alpha helical dimerization domain
- exposed hydrophobic leucine patches interacts with like domains on their dimerization partner
- zips the two TFs together in coil
What is the importance of leucine zipper (bZIP)
basic domains are stabley positioned to interact with DNA in the major groove
explain structure of helix loop helix (bHLH) DNA binding domain
compromises two alpha helical regions joined by unstructured polypeptide loop
- one alpha helix contains an exposed surface of hydrophobic amino acids making up the dimerization domain
- second contains basic domain
What do basic helix loop helix DNA binding domain facilitate
unstructured and flexible loop facilitates successful dimerization
What is epigenetics
changes in gene expression that can be retained through cell divisions but are caused by mechanisms other than changes in DNA sequence
What do post-translational histone modifications act as?
signals to regulate chromatin structure and DNA accessibility
What is euchromatin
transcriptionally active
- nucleosomes are further apart or
- has activating histone methylase
what is heterochromatin
transcriptionally repressed
- nucleosomes are more tighly pact hindering accessibility
- repressive histone methylase
What methylates almost all DNA on the cytosines of CpG sequence
DNA methyl transferase
How does methylation cause transcriptional repression
- 5 methylcytosine binds specialised methyl binding proteins
- chromatin remodelling enzymes recruited
- these help form transcriptionally repressed chromatin
- long term silencing of gene expression
What are house keeping genes
genes expressed in every cell type
What do promoter regions of house keeping genes contain?
has CpG islands: region of high densities of CpG motifs that are never methylated
- can only be silenced using chromatin remodelling
What happens to CpG islands associated with promerts of genes that will not be used
could be methylated
eg. somatic genes in sperm genes
what are tissue specific genes
specialized genes that are only expressed in certain cell types
How can tissue specific genes become transcriptionally active
must have their 5 methyl cytosine marks actively removed
What is imprinting
describes the phenomen by which certain genes are expressed in a parents of origin specific manner and is controlled by DNA methylation
What are Xist
non coding RNA that helps to inactivate one or more x chromosomes to form a barr body
An example is cell memory is Drosophila Eyeless gene. What does it do and what happens when a group of cells recieve a signal to activate Ey
- encodes a homeodomain TF that activates a cascade of gene expression required for its own continued expression (positive feedback)
- activation causes expression and division, where they retain memory of this signal
What are insulator elements
ensure that specific regulatory DNA sequences control gene promoters.(cannot act outside its domain)
They interact by DNA looping
What can IBP( insulator binding proteins)/insulator interaction do?
- block inappropriate interaction between a regulator sequence and a gene promoter (i.e. enhancer blocking)
- provide barrier to the spreading of neighbouring domain of transcriptionally inactive heterochromatin (i.e. barrier function)
What do the segments in embryo provide for the structured Drosophila adult?
progenitor cells
What segmentation genes are needed from the earliest stage of development of drosophilas
- Maternal genes
- gap genes
- Pair rule genes
- segment polarity genes
- homeotic (Hox) genes
What do maternal genes of drosophilas do
establish the anterior posterior axis of the body plan
Where is the bicoid mRNA localised
anterior
Where is the nanos mRNA localised
posterior
What do bicoid and nanons proteins do?
they extablish a gradient
- bicoid protiens bind caudal mRNA and inhibit thier translation leading to addition gradient formation
- nanons bind to hunch back mRNA (do same)
What activates the expression of gap genes and what is the conseqeunce
differing threshold concentraions of maternally provided TFs along the A-P axis
- mutations in gap genes lead to deletion of entire contigous body segments
What do mutations in pair rule genes lead to
embryos with half as many parasegments
What causes the expression of pair rule genes
flactuations in the relative concentrations of gap gene proteins along the A-P axis
What do pair rule genes do
regulate the expression of segment polarity genes that precisly refine the anterior posterior boundaries between the developing body segments
What do Segment polarity genes do
refine the segmental pattern established by the pair rule genes by defining the A-P segmental boundaries
What does the mutation of homeotic genes lead to
loss of correct identity in cells of a particular segment and therefore adoption of an incorrect identity
How are homeotic genes activated
under control of the gap genes and pair rule genes
What does the developmental pathway a cell within a particular cell segment takes depend on?
complement of homeotic genes expressed within it
- if homeotic gene is mutated then the functional complement is altered resulting in a different fate/identity
permanent record of cell position is established in early embryo genesis and is used much later in development in specify the correct adult structures. How is information retained?
- positive feedback loop by Hox genes self-regulation
- chromatin remodeling
- polycomb group (maintains repressed Hox genes
- trithorax group (maintains transcriptionally active Hox genes)
What gives the correct identity to the body segments along the anterior posterior axis during development
a transcription factor mediated hierachy of regulated gene expression
