Chapter 5: Regulation of Eukaryotic Gene Expression Flashcards

1
Q

Do histone acetylases favor gene expression or inactivate chromatin?

A

favor gene expression

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2
Q

Do histone deacetylases favor active or inactive chromatin?

A

inactive chromatin

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3
Q

How does histone acetylation cause gene expression?

A

certain lysyl residues in the histones are acetylated which decreases the positive charge and weakens the interaction with DNA

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4
Q

CCAAT is an upstream promoter element that binds what transcription factor?

A

NF-1

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5
Q

GC rich sequence is an upstream promotor that binds what general transcription factor?

A

SP-1

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6
Q

About how many base pairs away from the gene may an enhancer be?

A

1,000 bp away

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7
Q

Where may enhancers be located in relation to the gene they control?

A

may be located upstream, downstream, or within an intron of the gene they control

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8
Q

What is an example of an enhancer located in an intron?

A

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

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9
Q

What are cis regulators?

A

DNA regulatory base sequences (e.g. promoters, enhancers, response elements, and UPEs ) in the vicinity of genes that serve as binding sites for proteins?

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10
Q

What are “trans” regulators? Examples

A

transcription factors (and the genes that code for them)

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11
Q

What are transcription factors?

A

activator proteins that bind response elements

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12
Q

What are the 2 domains of transcription factors?

A

DNA-binding domain and an activation domain

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13
Q

Name some common DNA-binding domains.

A
  • Zinc fingers
  • Leucine zippers
  • Helix-loop-helix
  • helix-turn-helix
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14
Q

Name a common transcription factor receptor that has zinc finger motifs for its DNA binding site?

A

steroid hormone receptors

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15
Q

Name a common transcription factor that has leucine zippers as its DNA binding domain motif?

A

cAMP- dependent transcription factor

c-AMP response element binding (CREB)

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16
Q

Name a common transcription factor that has helix-turn-helix DNA binding domain motifs?

A

homeodomain proteins encoded by homeotic/ homeobox genes

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17
Q

What is another term for response element?

A

binding site (specific base pair sequence on DNA)

18
Q

What is the response element for steroid receptors to bind?

A

HRE (hormone response element)

19
Q

What is the response element for CREB protein to bind?

A

CRE

20
Q

What is the response element for PPARs to bind?

peroxisome proliferator activated receptors

A

PPREs

peroxisome proliferator respose elements)

21
Q

Function of PPARs? What is it activated by what substances?

A

regulate multiple aspects of lipid metabolism

activated by fibrates and thiazolidinediones, prostaglandin derivatives and fatty acids

22
Q

What type of DNA-bind domain motifs are characteristic of PPARs?

A

zinc fingers

23
Q

What are the response elements to which NFkB binds?

A

kB elements

24
Q

What is the purpose of general transcription factors?

A

they must bind to the promotor to allow RNA polymerase II to bind and form the initiation complex at the start site for transcription

25
Q

What does NFkB stand for?

A

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)

26
Q

Where do specific transcription factors bind?

A

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.

27
Q

What is the function of peroxisomes?

A

single-membrane organelles that accomplish B-oxidation of long and very long chain fatty acids similar to mitochondrial B-oxidation pathway

28
Q

What is Zellweger syndrome?

A

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

29
Q

What are characteristics of zellweger syndrome?

A

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

30
Q

How does Gemfibrozil work?

A

stimulates proliferation of peroxisomes and increases gene expression of LPL, resulting in the induction of the fatty acid oxidation pathway in these organelles

31
Q

What is the rate limiting step in the gluconeogenesis pathway?

A

PEPCK phosphoenolpyruvate carboxykinase

32
Q

Explain the steps for how cortisol induces PEPCK gene expression?

A
  1. cortisol diffuses into the hepatocyte, where it
  2. Binds to its receptor
  3. The complex enters the nucleus, and
  4. Binds (through the zinc fingers) to the glucocorticoid response element (GRE) associated with the PEPCK gene, which
  5. increase gene expression
  6. PEPCK concentration increases in the cell
  7. the rate of gluconeogenesis increases
33
Q

How does glucagon induce PEPCK gene expression?

A
  1. glucagon binds to a receptor in the cell membrane
  2. cAMP concentration increases
  3. PKA becomes active
  4. Phosphorylates and activates CREB
  5. Activated CREB enters the nucleus and binds to the CRE assoc. with the PEPCK gene
  6. PEPCK concentration increases in the cell
  7. The rate of gluconeogenesis increases
34
Q

Klein-Waardenburg syndrome is derived from a defect in what genes?

A

PAX-3 gene

35
Q

What are some symptoms of Klein Waardenburg syndrome?

A

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

36
Q

What is holoprosencephaly (HPE)? The defect?

A

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

37
Q

Abbreviation for Klein-Waardenburg syndrome?

A

WS-III

38
Q

What are some major exceptions to the rule of codominance?

A

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

39
Q

What is done to modify DNA which is cause of silencing genes in genetic imprinting?

A

methylation of DNA

40
Q

What are some clinical features of Prader Willi?

A

childhood obesity and hyperphagia

hypogonadotrophic hypogonadism

small hands and feet

intellectual disability

hypotonia

41
Q

What are the ways Prader Willi can be caused?

A

can result from uniparental (maternal) disomy of chromosome 15 or one inheriting a paternal chromosome in which region has been deleted.