5. Regulation of Eukaryotic Gene Expression Flashcards
Chromatin remodeling (4)
- Transcription factors (recruit coactivators such as histone actylases)
- Acetylation of lysyl residues in histones by acetylases (favor gene expression)
- Chromatin remodeling engine binds to acetylated lysine: expose promotor region
- Transcription factors bind promotor region and recruit RNA polymerase -> Transcription complex
Response elements
Enhancers/silencers, increase or decrease expression of a gene
Upstream promotor elements (2) + binding
CCAAT box (-75) binds transcription factor NF1 GC-richt sequence binds general transcription factor SP1
Enhancers are binding sites for..
Characteristics (5)
Activator proteins
- Up to 1000 bps away from gene
- Upstream, downstream or in intron
- Orientation is not important
- Tissue-specific possible
- Bending of DNA molecule -> closer to basal promotor region
Cis and trans regulatory elements
Cis: regulatory base sequences in DNA, serve as binding sites
Trans: transcription factors, can diffuse through cell
Two recognizable domains in transcription factors:
DNA-binding domain: binds to specific sequence
Activation domain
DNA-binding domains (4)
- Zinc fingers (steroid hormone receptors)
- Leucine zippers (cAMP-dep TF)
- Helix-loop-helix
- Helix-tunr-helix (homeodomain encoded by homeotic/homeobox genes)
Activation domain allows transcription factor to (3)
- Bind other TFs and coregulators
- Interact with RNAPII
- Recruit chromatin modifying proteins
Transcription factor -> Response element, function, protein class:
- Steroid receptors
- cAMP response element binding (CREB) protein
- Peroxisome proliferator-activated receptors (PPARs)
- NFkB
- Homeodomain proteins
- HRE - Steroid response - Zinc finger
- CRE - Response to cAMP - Leucine zipper
- PPREs - Lipid metabolism - Zinc finger
- kB elements - immune system - Rel domains
- — - development - Helix-turn-helix
General transcription factors needed for.. (2)
+ example
RNAP II binding and formation of initiation complex
Example: TFIID -> TATA box binding protein subunit (TBP) -> binds to TATA box
Specific transcription factors regulate the …
Rate of initiation of transcription
PPARs/PPREs activated by.. (4 examples)
Natural and xenobiotic ligands like
- Fatty acids
- Prostaglandin derivatives
- Fibrates
- Thiazolidinediones
Zellweger Syndrome
- Mutation
- Characteristics
- Mechanism
- Symptoms
- Mutation in genes of peroxisome biogenesis
- Deficiency peroxisomes, accumulation very long chain fatty acids and several unusual fatty acids
- Defect in fatty acid efflux
- Enlarged liver, high blood Cu and Fe, vision problems
- Children: growth and mental retardation, abnormal muscle tone
Peroxisomes
- Single membrane organelles that accomplish beta-oxidation of long and very long chain fatty acids, and oxidation of branded fatty acids and w-oxidation of ordinary fatty acids.
Gemfibrozil
- When prescribed
- Action
- Elevated triglycerides, normal cholesterol and LDL
- Stimulates peroxisomes and increases gene expression of lipoprotein lipase
Gluconeogenesis is activated by .. (2) + type of receptor
Glucagon (hypoglykemia, membrane-associated receptor)
Cortisol (stress, intracellular receptor Zn finger)
Sequence of Cortisol inducing PEPCK (phosphoenolpyruvate carboxykinase) expression, stimulates gluconeogenesis
- Cortisol binds to intracellular receptor
- Complex enters nucleus
- Binds (Zn fingers) to GRE (glucocorticoid response element) associated with PEPCK gene
- Increases gene expression
Sequence of Glucagon inducing PEPCK (phosphoenolpyruvate carboxykinase) expression, stimulates gluconeogenesis
- Glucagon binds cell membrane receptor
- Increase cAMP
- Activation Protein kinase A -> phosphorylates and activates CREB
- CREB enters nucleus, binds CRE associated with PEPCK gene
- Increases gene expression
Homeodomain proteins: what + genes?
+ Example
- Regulatory proteins in embryonic gene expression
- Homeobox (HOX) or homeotic genes
- Closely related: PAX (paired box)
Example: Klein-Waardenburg syndrome (WS-III)
Klein-Waardenburg Syndrome
- Mutation
- Symptoms/characteristics
PAX-3 mutation
Dystopia canthorum (lateral displacement inner corner eye)
Pigmentary abnormalities (frontal white blaze of hair, hypopigmentation skin, heterochromia irides)
Congenital deafness, limb abnormalities
Codominant expression
Two alleles (parental and maternal) expressed
Exceptions codominant expression
- Barr body (inactivated X-chromosome)
- Ig heavy and light chain loci
- T-cell receptor loci
Prader Willi syndrome
- Chromosome + inheritance
- Symptoms
- Chromosome 15, only paternal expressed (or maternal uniparental disomy)
- Childhood obesity and hyperplasia, hypogonadotrophic hypogonadism, small hands and feet, mental retardation, hypotonia
Genetic imprinting
Results in mono allelic expression, sometimes according to parent of origin
Methylation of DNA
Silences genes in genetic imprinting
Gene amplification
Often oncogenes
Membrane-bound vs secreted antibodies processing:
Due to alternative splicing
Sonic Hedgehog Gene mutations (haploinsufficiency = only one functional copy)
Holoprosencephaly (HPE)
Cerebral hemispheres fail to separate
