Chapter 5: Regulation of Eukaryotic Gene Expression

Question 1

Do histone acetylases favor gene expression or inactivate chromatin?

Answer 1

favor gene expression

Question 2

Do histone deacetylases favor active or inactive chromatin?

Answer 2

inactive chromatin

Question 3

How does histone acetylation cause gene expression?

Answer 3

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

Question 4

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

Answer 4

NF-1

Question 5

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

Answer 5

SP-1

Question 6

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

Answer 6

1,000 bp away

Question 7

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

Answer 7

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

Question 8

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

Answer 8

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

Question 9

What are cis regulators?

Answer 9

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

Question 10

What are “trans” regulators? Examples

Answer 10

transcription factors (and the genes that code for them)

Question 11

What are transcription factors?

Answer 11

activator proteins that bind response elements

Question 12

What are the 2 domains of transcription factors?

Answer 12

DNA-binding domain and an activation domain

Question 13

Name some common DNA-binding domains.

Answer 13

• Zinc fingers
• Leucine zippers
• Helix-loop-helix
• helix-turn-helix

Question 14

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

Answer 14

steroid hormone receptors

Question 15

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

Answer 15

cAMP- dependent transcription factor

c-AMP response element binding (CREB)

Question 16

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

Answer 16

homeodomain proteins encoded by homeotic/ homeobox genes

Question 17

What is another term for response element?

Answer 17

binding site (specific base pair sequence on DNA)

Question 18

What is the response element for steroid receptors to bind?

Answer 18

HRE (hormone response element)

Question 19

What is the response element for CREB protein to bind?

Answer 19

CRE

Question 20

What is the response element for PPARs to bind?

peroxisome proliferator activated receptors

Answer 20

PPREs

peroxisome proliferator respose elements)

Question 21

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

Answer 21

regulate multiple aspects of lipid metabolism

activated by fibrates and thiazolidinediones, prostaglandin derivatives and fatty acids

Question 22

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

Answer 22

zinc fingers

Question 23

What are the response elements to which NFkB binds?

Answer 23

kB elements

Question 24

What is the purpose of general transcription factors?

Answer 24

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

Question 25

What does NFkB stand for?

Answer 25

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

Question 26

Where do specific transcription factors bind?

Answer 26

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.

Question 27

What is the function of peroxisomes?

Answer 27

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

Question 28

What is Zellweger syndrome?

Answer 28

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

Question 29

What are characteristics of Zellweger syndrome?

Answer 29

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

Question 30

How does Gemfibrozil work?

Answer 30

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

Question 31

What is the rate limiting step in the gluconeogenesis pathway?

Answer 31

PEPCK phosphoenolpyruvate carboxykinase

Question 32

Explain the steps for how cortisol induces PEPCK gene expression?

Answer 32

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

Question 33

How does glucagon induce PEPCK gene expression?

Answer 33

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

Question 34

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

Answer 34

PAX-3 gene

Question 35

What are some symptoms of Klein Waardenburg syndrome?

Answer 35

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

Question 36

What is holoprosencephaly (HPE)? The defect?

Answer 36

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

Question 37

Abbreviation for Klein-Waardenburg syndrome?

Answer 37

WS-III

Question 38

What are some major exceptions to the rule of codominance?

Answer 38

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

Question 39

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

Answer 39

methylation of DNA

Question 40

What are some clinical features of Prader Willi?

Answer 40

childhood obesity and hyperphagia hypogonadotrophic hypogonadism small hands and feet intellectual disability hypotonia

Question 41

What are the ways Prader Willi can be caused?

Answer 41

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