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