Regulation of gene expression

Question 1

what are three reasons for gene regulation?

Answer 1

adaptation

development

conservation of energy

Question 2

A Zinc finger is the target of a drug. What is being stopped inside the cell?

Answer 2

Zinc finger = protein motiff

1. each of two Zn fingers of the estrogen receptor contains Zn ion coordinated with 4 cysteine residues
2. binds a specfic DNA in the major groove- nucleotide recognition signal

Question 3

elucidate the mechanism of mRNA editing on protein function

Question 4

regulation of Gene expression in prokaryotes. give three scenerios

Answer 4

1. Lac operon
   
   1. No glucose/ lactose–or—only glucose
      
      1. no Lac operon
   2. Glucose and Lactose
      
      1. Increase Lac operon expression
      2. No cAMP-CRP expression
         
         1. w/o coactivator transcription is low
   3. No glucose but Yes to Lactose
      
      1. allolactose activates repressor
      2. increase Lac operon
      3. Yes cAMP-CRP

Question 5

when Trp is high in the bacterial cell the Trp expression is

Answer 5

low, b/c Trp is a corepressor. terminates transcription

Question 6

what can activate a set of genes?

Answer 6

inducer-

Question 7

what can activate many genes with common regulatory elements?

Answer 7

Transcription factor

Question 8

what is the transcription level of the DNA when part of the promoter on a nucleosome?

Answer 8

there will be no transcription if a promoter region is a part of a nuclesome

Question 9

when genes are activly transcribed only on paternally or maternally inherited chromosomes

Answer 9

genetic imprinting

Question 10

what occurs when the lysine are methylated and acetylated?

Answer 10

gene expression occurs

Question 11

what happens when lysine is acetylated and serine is phosphorylated?

Answer 11

genes are expressed

Question 12

what occurs in histones for heterochromatin and silencing of gene expression?

Answer 12

methylation of the lysine

Question 13

trimethylation of H3 lysine9 attracts

Answer 13

heterochromatin-specific protein (HP1)

which induces a spreadin wave of Lys9 trimethylation followed by further HP1 binding

Question 14

what is involved in increasing and decreasing acetylation in histones?

Answer 14

HATs -add acetyl groups on

HDACs - remove acetyl groups

Question 15

inactivation of the X c’some in a female is an exapmle of

Answer 15

genetic imprinting

Question 16

After examining the chromosomes of a patient you see excessive silencing of genes on both copies of the chromosome 15. The child has an insatiable appetite and low muscle tone

Answer 16

prader willi syndrome-

• paternal c’some 15 is silenced.
• this is a complication because the maternal 15 csome is normally silenced
• three possible scenerios
  
  • imprinting- 1%
  • maternal uniparental disomy 29%
  • deletion of paternal region 70%

Question 17

A child has severe intellectual and developmental delays, but otherwise seems fine. A genetic analysis shows that certain genes have been silenced on c’some 15, but only in the brain.

Answer 17

angel man syndrome

1. caused by inability to express UBE3A on paternally inherited c’some
2. both copies are needed for normal developement, certain regions of the brain are affected by the paternal silencing
3. causes
   
   1. imprinting defect 2-4%
   2. uniparental disomy 2%
   3. deletion 70%
   4. gene mutation-10%
   5. unknown 15%

Question 18

a person was diagnosed with russel silver syndrome, what c’somes are affected and how?

Answer 18

type of dwarfism

• 11 -60%
  
  • hypomethylation of maternally expressed H19 and paternally expressed IGF2
• 7-10%
  
  • maternal uniparental disomy

Question 19

a cancers genome was analyzed at the epigenetic level, what could expect to see?

Answer 19

1. global hypomethylation

normally

• hypermethylation- silence tumor supressors
• hypomethylation-activate proto oncogenes:cMYC and H-RAS

Question 20

When given a dosage of steroids where does this medication have the greatest effect in a cell?

Answer 20

many lipophilic hormones regulate transcription throug hnuclear receptors

1. NC= gene specific TFs
   2.

Question 21

regulation of trascription facors

Answer 21

1. increase/decrease amount of TF
2. binding of inhibitor or stimulator
3. modulation of nuclear entry
4. posttranslational modifications
   
   1. phosphorylation of CREB by PKA or MAP kinase

Question 23

what receptor must be activated to produce the following?

1. metabolism
2. development
3. immune response

Answer 23

glucocorticoid receptor

Question 24

Activation of this transcription factor leads to the following

1. apoptosis
2. differentiation
3. DNA damage

Answer 24

TF specificity protein 1

Question 25

Describe the series of steps followed by cortisol entering the cell

Answer 25

1. binds to glucocorticoid receptor in the cytosol
2. HSP disociates from
   
   1. results in exposing nuclear localization signals
3. glu…receptors dimmerize and go into the nucleus, binding to glucocorticoid response element
4. GRE activates transcription involved in
   
   1. metabolism
   2. development
   3. immune response

Question 26

what is unique about the Thyroid receptor?

Answer 26

the thyroid receptor is bound constitutively with the retinoid receptors

1. w/o thyroid hormone
   
   1. dimer binds the corepressor and inhibits transcription
2. hormone bound
   
   1. dimer binds the coactivator and activates transcription process

Question 27

A woman gives birth to a phenotypically seen female but after examining the karyotype, they are told the child is male (XY). Explain the syndorme and the process-

Answer 27

Androgen receptor syndromew

• males are producing enough androgens but the nuclear receptor is not working properly
  
  • reduced sensitivity to androgens

this is an x-linked,

Question 28

A patient with beta thallasemia is sent for genetic diagnostics. The results show that the TATA box is fine for the gene. What else could lead to this phenotype?

Answer 28

Locus control regions

1. DNA elements that associate with proteins to control the expression of a cluster of genes
2. LCRs contol the expression of globin gene family

This patient could have a deletion in the LCR, leading to a down regulation of the B globin gene

Question 29

Jimmy is studying genetics and has drawn all the genes right next to eachother and wonders, how come they don’t all ge transcribed at the same time?

Answer 29

He has forgotten about Insulators, which prevent such cross talk and function to compartmentalize the genome into discrete regulatory domains.

1. boundaries of elements that associate with proteins that act as
   
   1. enhancer blockers- when located between enhancer and promoter
   2. barriers- when located between silencer and promoter

Question 30

What does the hundreds of rRNA and tRNA genes stand as an exapmle for? What is an unfortuante consequence from this required item?

Answer 30

gene amplification

1. amplified genes provide multiple sites for gene transcription

frequent genetic abnormality in human cancer cells, which consists of multiple extra copies of a specific region of DNA.

1. amplified genes here are oncognes** and **drug restistance genes
   
   1. _​_example of drug resistance if _DIHYDROFOLATE REDUCTASE_ gene increases in number to target methotrexate in malignant cells
2. MYC, RAS, EGFR and FGF

Question 31

what % of genes are ALTERNATIVLY spliced in the human gneome

Answer 31

80%

Question 32

Enhancer blocker are between?

Answer 32

enhancer and promoter

Question 33

Barriers are between?

Answer 33

silencer and promoter

Question 34

what is the most common type of alternative splicing? Explain it

Answer 34

exon skipping is the most common of the alternative splicings of mRNA

1. notice in the picture that skipping two introns means splicing out an intron as well.

Question 35

compare constituitive splicing to alternative

Question 36

Explain the alternative splicing using the calcitonin gene as an example.

where? purpose? disease association with malfunction?

Answer 36

calcitonin gene produces two different mRNAs for two different proteins.

1. consituitive splicing=calcitonin
   
   1. where?
      
      1. thyroid cells
   2. purpose
      
      1. reduces plasma calcium levels
   3. disease
      
      1. increased level associated with thyroid nodule carcinoma
2. exon skipping=calcitonin gene related protein (CGRP)
   
   1. where?
      
      1. neurons
   2. purpose
      
      1. peptide vasodilator and pain transmittor
   3. disease
      
      1. increased levels are associated with migraines

Question 37

a patient is diagnosed with frontotemporal dementia with parkinsonism. Explain the possible disease and associated mechanism

Answer 37

tauopathies

1. diseases of the central nervous system that show abnormal intracellular accumulations of abnormal filaments that contain the microtubule associated Tau protein.
2. mutation in the tau gene affect splicing of the gene and there for the end product.

Question 38

A 25 year female has high LDL. Her mother, 76 post menapausal does not have high LDL.

A family genetic counselor sees the same mutation in both of the women. What could cause the disease phenotype to vary?

Answer 38

1. LDL receptor splicing variants caused by a single nucleotide polymorphism are sex-specific foactor for hypercholesterolemia
2. the mutation promotes exon skipping in the liver of
   
   1. pre-menapausal women
   2. but not
      
      1. affect on post menapausal women
      2. or men

Question 39

list five triggers of mRNA degradation and the degrading component.

what inherent component of the mRNA strand can slow down translation?

Answer 39

1. mRNA turnover- loss of tail -> rapid degradation
   
   1. cytoplasmic exosome-3’end
2. ARE-mediated decay- occurs on mRNAs containing A+U rich elements (limits the half life of mRNA to prevent overexpression)
   
   1. cytoplasmic exosome-3’end
3. Nonstop decay- assists in degradation of mRNA that lacks translation termination codon
   
   1. cytoplasmic exosome- 3’ end
4. nonsense-mediated-degradation is trggered when ribosome stops before reaching an original stop codon
   
   1. binding of ribosome to mRNA
5. miRNA-can target mRNA for degradation
6. Rare codons- are used to regulate the rate of translation
   
   1. have fewer copies of tRNA in the cell
   2. it can slow down translation
   3. they usually are located at the begining of the coding region of mRNA

Question 40

describe the affect that high and low iron conditions manipulate in the cell

Answer 40

Ferritin is the main iron storage protein with cells

1. contains an iron response element for two intracellular conditions
   
   1. low iron
      
      1. IRE-BP attaches to IRE and prevents translation
   2. high iron
      
      1. IRE-BP binds iron
      2. dissociates from IRE
      3. translation of ferritin mRNA

Transferrin receptor- takes up transferrin

1. two intracellular conditions
   
   1. low iron
      
      1. IRE-BP binds to IRE and prevents degradation of mRNA
      2. leads to translation of more
   2. high iron
      
      1. IRE-BP binds to iron
      2. releases mRNA
      3. mRNA is degraded and less transferritin receptor is made

Question 41

summarize the gene expression in prokaryotes :

through the induction and repression of transcription using:

Answer 41

1. repressors
2. inducers
3. corepressors
4. coactivators

Question 42

summarize the regulation of gene expression in eukaryote

Answer 42

1. chromatin modification and remodeling
   
   1. HATs and HDACs
   2. DNA and histone methyltransferases and demethylases
2. LCRs and Insulators
3. Gene amplification and rearangments
4. regulation of transcription initiation
   
   1. positive and negative transcription factors
5. on the level of translation
   
   1. mRNA editing(splicing)
   2. mRNA degradation (CytoExosome)
   3. binding of ribosome to mRNA (NMD)