Chapter 5: Regulation of Eukaryotic Gene Expression Flashcards
Do histone acetylases favor gene expression or inactivate chromatin?
favor gene expression
Do histone deacetylases favor active or inactive chromatin?
inactive chromatin
How does histone acetylation cause gene expression?
certain lysyl residues in the histones are acetylated which decreases the positive charge and weakens the interaction with DNA
CCAAT is an upstream promoter element that binds what transcription factor?
NF-1
GC rich sequence is an upstream promotor that binds what general transcription factor?
SP-1
About how many base pairs away from the gene may an enhancer be?
1,000 bp away
Where may enhancers be located in relation to the gene they control?
may be located upstream, downstream, or within an intron of the gene they control
What is an example of an enhancer located in an intron?
the Ig heavy chain locus has an enhancer in the large intron separating the coding regions for the variable domain from the coding regions for the constant domain
What are cis regulators?
DNA regulatory base sequences (e.g. promoters, enhancers, response elements, and UPEs ) in the vicinity of genes that serve as binding sites for proteins?
What are “trans” regulators? Examples
transcription factors (and the genes that code for them)
What are transcription factors?
activator proteins that bind response elements
What are the 2 domains of transcription factors?
DNA-binding domain and an activation domain
Name some common DNA-binding domains.
- Zinc fingers
- Leucine zippers
- Helix-loop-helix
- helix-turn-helix
Name a common transcription factor receptor that has zinc finger motifs for its DNA binding site?
steroid hormone receptors
Name a common transcription factor that has leucine zippers as its DNA binding domain motif?
cAMP- dependent transcription factor
c-AMP response element binding (CREB)
Name a common transcription factor that has helix-turn-helix DNA binding domain motifs?
homeodomain proteins encoded by homeotic/ homeobox genes
What is another term for response element?
binding site (specific base pair sequence on DNA)
What is the response element for steroid receptors to bind?
HRE (hormone response element)
What is the response element for CREB protein to bind?
CRE
What is the response element for PPARs to bind?
peroxisome proliferator activated receptors
PPREs
peroxisome proliferator respose elements)
Function of PPARs? What is it activated by what substances?
regulate multiple aspects of lipid metabolism
activated by fibrates and thiazolidinediones, prostaglandin derivatives and fatty acids
What type of DNA-bind domain motifs are characteristic of PPARs?
zinc fingers
What are the response elements to which NFkB binds?
kB elements
What is the purpose of general transcription factors?
they must bind to the promotor to allow RNA polymerase II to bind and form the initiation complex at the start site for transcription
What does NFkB stand for?
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)
Where do specific transcription factors bind?
to enhancer regions or, in a few cases, to silencers and modulate the formation of the initiation complex, thus regulating the rate of initiation of transcription.
What is the function of peroxisomes?
single-membrane organelles that accomplish B-oxidation of long and very long chain fatty acids similar to mitochondrial B-oxidation pathway
What is Zellweger syndrome?
a genetic disease caused by a mutation in any one of several genes (locus heterogeneity) involved in peroxisome biogenesis
Mechanism: defect in fatty acid efflux from peroxisomes
What are characteristics of Zellweger syndrome?
characterized by a deficiency of peroxisomes which cause an accumulation of long chain fatty acids and several unusual fatty acids (e.g. hydroxylated and branched fatty acids)
most common features are enlarged liver, high blood levels of Cu and Fe, and vision problems
In affected infants: failure to grow, intellectual disability,and multiple developmental abnormalities; abnormal muscle tone
infants usually die within first year
How does Gemfibrozil work?
stimulates proliferation of peroxisomes and increases gene expression of LPL, resulting in the induction of the fatty acid oxidation pathway in these organelles
What is the rate limiting step in the gluconeogenesis pathway?
PEPCK phosphoenolpyruvate carboxykinase
Explain the steps for how cortisol induces PEPCK gene expression?
- cortisol diffuses into the hepatocyte, where it
- Binds to its receptor
- The complex enters the nucleus, and
- Binds (through the zinc fingers) to the glucocorticoid response element (GRE) associated with the PEPCK gene, which
- increase gene expression
- PEPCK concentration increases in the cell
- the rate of gluconeogenesis increases
How does glucagon induce PEPCK gene expression?
- glucagon binds to a receptor in the cell membrane
- cAMP concentration increases
- PKA becomes active
- Phosphorylates and activates CREB
- Activated CREB enters the nucleus and binds to the CRE assoc. with the PEPCK gene
- PEPCK concentration increases in the cell
- The rate of gluconeogenesis increases
Klein-Waardenburg syndrome is derived from a defect in what genes?
PAX-3 gene
What are some symptoms of Klein Waardenburg syndrome?
dystopia canthorum (lateral displacement of the inner corner of the eye
pigmentary abnormalities (frontal white blaze of hair, patchy hypopigmentation of the skin, heterochromia irides
congenital deafness
limb abnormalities
What is holoprosencephaly (HPE)? The defect?
common developmental anomaly of the human forebrain and midface, where the cerebral hemisphere fail to separate into distinct left and right halves
insufficiency for sonic hedgehog (SHH) is the cause
Abbreviation for Klein-Waardenburg syndrome?
WS-III
What are some major exceptions to the rule of codominance?
On Barr body (inactivated X chromosome) in women
In immunoglobulin heavy and light chain loci (ensuring that one B cell makes only one specific of antibody
In T cell receptor loci
What is done to modify DNA which is cause of silencing genes in genetic imprinting?
methylation of DNA
What are some clinical features of Prader Willi?
childhood obesity and hyperphagia
hypogonadotrophic hypogonadism
small hands and feet
intellectual disability
hypotonia
What are the ways Prader Willi can be caused?
can result from uniparental (maternal) disomy of chromosome 15 or one inheriting a paternal chromosome in which region has been deleted.
