5. Regulation of Eukaryotic Gene Expression Flashcards

1
Q

Chromatin remodeling (4)

A
  • 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
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2
Q

Response elements

A

Enhancers/silencers, increase or decrease expression of a gene

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3
Q

Upstream promotor elements (2) + binding

A
CCAAT box (-75) binds transcription factor NF1
GC-richt sequence binds general transcription factor SP1
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4
Q

Enhancers are binding sites for..

Characteristics (5)

A

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
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5
Q

Cis and trans regulatory elements

A

Cis: regulatory base sequences in DNA, serve as binding sites
Trans: transcription factors, can diffuse through cell

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6
Q

Two recognizable domains in transcription factors:

A

DNA-binding domain: binds to specific sequence

Activation domain

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7
Q

DNA-binding domains (4)

A
  • Zinc fingers (steroid hormone receptors)
  • Leucine zippers (cAMP-dep TF)
  • Helix-loop-helix
  • Helix-tunr-helix (homeodomain encoded by homeotic/homeobox genes)
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8
Q

Activation domain allows transcription factor to (3)

A
  • Bind other TFs and coregulators
  • Interact with RNAPII
  • Recruit chromatin modifying proteins
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9
Q

Transcription factor -> Response element, function, protein class:

  1. Steroid receptors
  2. cAMP response element binding (CREB) protein
  3. Peroxisome proliferator-activated receptors (PPARs)
  4. NFkB
  5. Homeodomain proteins
A
  1. HRE - Steroid response - Zinc finger
  2. CRE - Response to cAMP - Leucine zipper
  3. PPREs - Lipid metabolism - Zinc finger
  4. kB elements - immune system - Rel domains
  5. — - development - Helix-turn-helix
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10
Q

General transcription factors needed for.. (2)

+ example

A

RNAP II binding and formation of initiation complex

Example: TFIID -> TATA box binding protein subunit (TBP) -> binds to TATA box

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11
Q

Specific transcription factors regulate the …

A

Rate of initiation of transcription

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12
Q

PPARs/PPREs activated by.. (4 examples)

A

Natural and xenobiotic ligands like

  • Fatty acids
  • Prostaglandin derivatives
  • Fibrates
  • Thiazolidinediones
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13
Q

Zellweger Syndrome

  • Mutation
  • Characteristics
  • Mechanism
  • Symptoms
A
  • 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
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14
Q

Peroxisomes

A
  • 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.
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15
Q

Gemfibrozil

  • When prescribed
  • Action
A
  • Elevated triglycerides, normal cholesterol and LDL

- Stimulates peroxisomes and increases gene expression of lipoprotein lipase

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16
Q

Gluconeogenesis is activated by .. (2) + type of receptor

A

Glucagon (hypoglykemia, membrane-associated receptor)

Cortisol (stress, intracellular receptor Zn finger)

17
Q

Sequence of Cortisol inducing PEPCK (phosphoenolpyruvate carboxykinase) expression, stimulates gluconeogenesis

A
  • Cortisol binds to intracellular receptor
  • Complex enters nucleus
  • Binds (Zn fingers) to GRE (glucocorticoid response element) associated with PEPCK gene
  • Increases gene expression
18
Q

Sequence of Glucagon inducing PEPCK (phosphoenolpyruvate carboxykinase) expression, stimulates gluconeogenesis

A
  • 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
19
Q

Homeodomain proteins: what + genes?

+ Example

A
  • Regulatory proteins in embryonic gene expression
  • Homeobox (HOX) or homeotic genes
  • Closely related: PAX (paired box)
    Example: Klein-Waardenburg syndrome (WS-III)
20
Q

Klein-Waardenburg Syndrome

  • Mutation
  • Symptoms/characteristics
A

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

21
Q

Codominant expression

A

Two alleles (parental and maternal) expressed

22
Q

Exceptions codominant expression

A
  • Barr body (inactivated X-chromosome)
  • Ig heavy and light chain loci
  • T-cell receptor loci
23
Q

Prader Willi syndrome

  • Chromosome + inheritance
  • Symptoms
A
  • Chromosome 15, only paternal expressed (or maternal uniparental disomy)
  • Childhood obesity and hyperplasia, hypogonadotrophic hypogonadism, small hands and feet, mental retardation, hypotonia
24
Q

Genetic imprinting

A

Results in mono allelic expression, sometimes according to parent of origin

25
Q

Methylation of DNA

A

Silences genes in genetic imprinting

26
Q

Gene amplification

A

Often oncogenes

27
Q

Membrane-bound vs secreted antibodies processing:

A

Due to alternative splicing

28
Q

Sonic Hedgehog Gene mutations (haploinsufficiency = only one functional copy)

A

Holoprosencephaly (HPE)

Cerebral hemispheres fail to separate