Lecture 9-10: gene expression control Flashcards

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1
Q

If all cells have the same genome then what contributes to cell differentiation?

A

changes in gene expression

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2
Q

What are post transcription factors that affect gene expression?

A
  • alternative splicing

- post translational modifications

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3
Q

What is required in gene regulation?

A
  • short DNA sequence for recognition site of DNA binding protein
  • gene regulatory proteins which bind and activate gene
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4
Q

What is a dimerization module responsible for, on a transcription factor?

A
  • forms dimer with other proteins subunits
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5
Q

What is an activation module?

A

area that allows a gene to be turned on

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6
Q

What is a regulatory module?

A

region on DNA that allows transcription factor regulation

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7
Q

Describe a helix-turn-helix DNA binding domain.

A
  • simple and most common
  • symmetric dimers
  • the alpha helices are connected by short chain of amino acids
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8
Q

Where does the zinc-finger domain bind?

A

major groove of DNA

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9
Q

What is the role of the Zn finger domain?

A
  • stabilize interactions with DNA by forming tandem clusters
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10
Q

What are the amino acids that form a bond between DNA and the Zn finger domain?

A
  • Arg

- His

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11
Q

What regions are located on the leucine zipper motif?

A
  • dimerization domain
  • activation domain
  • DNA binding domain
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12
Q

How strong of interaction do the alpha helices that form the leucine zipper have?

A
  • bonds forms every 7 amino acids

- pinching DNA between the two strands

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13
Q

What are the domains of the helix-loop-helix domain?

A
  • DNA binding
  • dimerization domain
  • activation domain
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14
Q

What is the structure of the helix-loop-helix domain?

A

a short alpha chain, connected by a loop to a longer second alpha chain

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15
Q

What is hereditary spherocytosis?

A
  • hemolytic anemia with spherical and fragile RBC
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16
Q

What causes hereditary spherocytosis?

A
  • gene mutation for erythrocyte membrane skeleton, not making enough proteins
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17
Q

The erythrocyte membrane skeleton has what properties?

A

confers durability and stability to RBCs

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18
Q

What is the normal function of KLF1?

A
  • binds to DNA, unwinds and causes transcription
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19
Q

What happens with the HS mutated KLF1?

A
  • binds to the opposite strand of DNA, preventing unwinding
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20
Q

How can transcription factors be identified?

A
  • gel mobility/ Electrophoretic Mobility Shift Assay

- Affinity Chromatography

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21
Q

What is CHIP?

A
  • chromatin immuno-precipitation

- identifies the sites in a genome that known regulatory proteins bind

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22
Q

What is the gene control region of DNA?

A
  • region that regulates and initiates transcription

- promoter is included

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23
Q

What assembles at the promoter region of DNA?

A

RNA pol and general transcription factors

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24
Q

Which is easier to remove histones from DNA?

A

acetylated

- this and nucleosome remodeling increases accessibility of DNA to proteins and favors transcription

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25
Q

What does chromatin remodeling complex binding to DNA allow?

A

nucleosomes slide and allow access to transcription

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26
Q

What does the presence of histone chaperones allow?

A
  • histone chaperones cause the removal of histones, allowing greater acces to the nucleosomal DNA
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27
Q

What happens when histone modifying complex binds to DNA?

A
  • cause destabilization of histone complexes and attract transcription factors
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28
Q

What is the effect of methylating the histone complex?

A
  • methylation leads to silencing of the chromatin
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29
Q

How are gene regulatory proteins controlled?

A
  • synthesis
  • ligand binding
  • covalent modification phosphorylation
  • addition of subunits
  • unmasking
  • nuclear entry
  • proteolysis
30
Q

What composes embryonic hemoglobin and when does this change to fetal Hb?

A
  • zeta and epsilon

- changes at 10 wk

31
Q

What composes fetal Hb and when does it convert to adult?

A
  • alpha and gamma

- loss of gamma begins at birth

32
Q

What composes adult Hb and when does it begin to form?

A
  • alpha and beta

- beta begins to form at birth along with delta

33
Q

What ways can positive and negative control have on alternative splicing?

A
  • positive will promote splicing with an activator

- negative will prevent by using a repressor

34
Q

Spatial localization of mRNA occurs via what mechanisms after leaving the nucleus via pores?

A
  1. mRNA travel to destination vie cytoskeletal motors
  2. random diffusion and trapping
  3. random movement and degradation (allows RNA that is not trapped to be degraded)
35
Q

At what point will the poly A tail no longer be effective at preventing mRNA degradation?

A

around 25 nucleotides long leads to mRNA sequence degradation

36
Q

What is decapping?

A

mRNA is degraded from the 5’ end bc the cap was removed

37
Q

What is the role and regulation of the transferrin receptor?

A
  • helps import iron into the cell

- low [iron] promotes increased expression of the transferrin-receptor

38
Q

Slide 12 lecture 10

A

Draw out the iron cycle

39
Q

Where is excess iron mainly stored?

A
  • liver
  • lungs
  • pancreas
40
Q

What is ferritin?

A

intracellular protein that binds ferric iron

41
Q

What happens to ferritin mRNA in iron starvation?

A

-the cells do not need to store iron and form more TfR mRNA

42
Q

What happens to ferritin mRNA when iron is in excess?

A
  • promotes need to store iron
  • mRNA of ferritin increases
  • mRNA of TfR is reduced
43
Q

If iron regulatory proteins bind to iron responsive elements at the 5’ region of mRNA what happens?

A

no ferritin is formed

44
Q

What are microRNAs?

A

repressors of gene activity

45
Q

What is an RNA-induced silencing complex?

A

RISC that is formed from argonaute and other proteins

46
Q

Are the changes in microRNA expression causative of disease or responsive to disease?

A

yes.

47
Q

What is a causative mutation?

A

miRNAs that are likely to have mutations that cause disease

48
Q

What is a responsive mutation?

A

Caused my increased miRNA expression that down regulates genes in response to disease to limit severity

49
Q

What variant of what gene is associated with tourette’s syndrome?

A

SLITRK1

50
Q

Is tourette’s syndrome upregulate or downregulate the expression of SLITRK1?

A

downregulation via miR-189

51
Q

What steps are required to produce a properly functioning protein?

A
  • post translational modifications
  • 3D folding with help from molecular chaperones
  • binding of co-factors
52
Q

Molecular chaperones also have what function?

A

heat shock proteins that increase synthesis with temperature increase

53
Q

Why does temperature increase lead to increase in chaperones?

A
  • increased temperature causes increased misfolding of proteins
54
Q

What are the major families of heat shock proteins?

A

Hsp60 and Hsp 70

55
Q

What are functions of the proteasome?

A
  • degrade improper folded proteins
  • destroy aberrant proteins
  • controls protein activity
56
Q

What is the specificity that allows for proteasomes to bind?

A

two E1 ubiquitin enzymes and 1 proteasome

57
Q

What is bortexomib?

A

powerful proteasome inhibitor

58
Q

What is a myeloma and what is the best way to treat it?

A
  • cancer in plasma cells

- treated with proteasome inhibitors

59
Q

In what ways can ubiquitin ligase be activated?

A
  • phosphorylation by protein kinase
  • allosteric transition by ligand binding
  • allosteric transition by protein subunit addition
60
Q

In what ways is a degradation signal activated?

A
  • phosphorylation by protein kinase
  • protein dissociation that unmasks a certain region
  • creating a destabilizing N-terminus
61
Q

What are the effects of glucocorticoid cortisol?

A
  • response to stress
  • raise BG
  • aid with fat, protein, carb metabolism
  • diurnal
62
Q

When will glucocorticoid cortisol levels be high and low?

A
  • high: 8 am

- low: midnight

63
Q

What is the effect of methyl groups adding to DNA?

A
  • DNA methylation leads to repressing gene expression
64
Q

Is methylation of the parent strand conserved on the daughter strands after replication?

A

yes, it may have to undergo a second round of methylation, but the final strand will be indentical to the parental

65
Q

What is genomic Imprinting?

A
  • differential expressio nof genetic material depending on the parent of origin
66
Q

What is epigenetics?

A
  • regulation of expression of gene activity without altering gene structure, such as methylation
67
Q

What prader willi syndrome?

A
  • caused by paternal deletion on chromosome 15
68
Q

What is stage one of prader willi?

A
  • infantile hypotonia
  • poor suck
  • feeding difficulties
  • failure to thrive
69
Q

What is stage two of prader willi?

A
  • hyperphagia

- onset of early childhood obesity

70
Q

What causes prader willi syndrome?

A
  • deletion of the paternal 15q11-q13, which is an inherited deletion on chromosome 15 from paternal