Lecture 9-10: gene expression control Flashcards Preview

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Flashcards in Lecture 9-10: gene expression control Deck (70):
1

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

changes in gene expression

2

What are post transcription factors that affect gene expression?

- alternative splicing
- post translational modifications

3

What is required in gene regulation?

- short DNA sequence for recognition site of DNA binding protein
- gene regulatory proteins which bind and activate gene

4

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

- forms dimer with other proteins subunits

5

What is an activation module?

area that allows a gene to be turned on

6

What is a regulatory module?

region on DNA that allows transcription factor regulation

7

Describe a helix-turn-helix DNA binding domain.

- simple and most common
- symmetric dimers
- the alpha helices are connected by short chain of amino acids

8

Where does the zinc-finger domain bind?

major groove of DNA

9

What is the role of the Zn finger domain?

- stabilize interactions with DNA by forming tandem clusters

10

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

- Arg
- His

11

What regions are located on the leucine zipper motif?

- dimerization domain
- activation domain
- DNA binding domain

12

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

- bonds forms every 7 amino acids
- pinching DNA between the two strands

13

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

- DNA binding
- dimerization domain
- activation domain

14

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

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

15

What is hereditary spherocytosis?

- hemolytic anemia with spherical and fragile RBC

16

What causes hereditary spherocytosis?

- gene mutation for erythrocyte membrane skeleton, not making enough proteins

17

The erythrocyte membrane skeleton has what properties?

confers durability and stability to RBCs

18

What is the normal function of KLF1?

- binds to DNA, unwinds and causes transcription

19

What happens with the HS mutated KLF1?

- binds to the opposite strand of DNA, preventing unwinding

20

How can transcription factors be identified?

- gel mobility/ Electrophoretic Mobility Shift Assay
- Affinity Chromatography

21

What is CHIP?

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

22

What is the gene control region of DNA?

- region that regulates and initiates transcription
- promoter is included

23

What assembles at the promoter region of DNA?

RNA pol and general transcription factors

24

Which is easier to remove histones from DNA?

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

25

What does chromatin remodeling complex binding to DNA allow?

nucleosomes slide and allow access to transcription

26

What does the presence of histone chaperones allow?

- histone chaperones cause the removal of histones, allowing greater acces to the nucleosomal DNA

27

What happens when histone modifying complex binds to DNA?

- cause destabilization of histone complexes and attract transcription factors

28

What is the effect of methylating the histone complex?

- methylation leads to silencing of the chromatin

29

How are gene regulatory proteins controlled?

- synthesis
- ligand binding
- covalent modification phosphorylation
- addition of subunits
- unmasking
- nuclear entry
- proteolysis

30

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

- zeta and epsilon
- changes at 10 wk

31

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

- alpha and gamma
- loss of gamma begins at birth

32

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

- alpha and beta
- beta begins to form at birth along with delta

33

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

- positive will promote splicing with an activator
- negative will prevent by using a repressor

34

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

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

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

around 25 nucleotides long leads to mRNA sequence degradation

36

What is decapping?

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

37

What is the role and regulation of the transferrin receptor?

- helps import iron into the cell
- low [iron] promotes increased expression of the transferrin-receptor

38

Slide 12 lecture 10

Draw out the iron cycle

39

Where is excess iron mainly stored?

- liver
- lungs
- pancreas

40

What is ferritin?

intracellular protein that binds ferric iron

41

What happens to ferritin mRNA in iron starvation?

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

42

What happens to ferritin mRNA when iron is in excess?

- promotes need to store iron
- mRNA of ferritin increases
- mRNA of TfR is reduced

43

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

no ferritin is formed

44

What are microRNAs?

repressors of gene activity

45

What is an RNA-induced silencing complex?

RISC that is formed from argonaute and other proteins

46

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

yes.

47

What is a causative mutation?

miRNAs that are likely to have mutations that cause disease

48

What is a responsive mutation?

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

49

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

SLITRK1

50

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

downregulation via miR-189

51

What steps are required to produce a properly functioning protein?

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

52

Molecular chaperones also have what function?

heat shock proteins that increase synthesis with temperature increase

53

Why does temperature increase lead to increase in chaperones?

- increased temperature causes increased misfolding of proteins

54

What are the major families of heat shock proteins?

Hsp60 and Hsp 70

55

What are functions of the proteasome?

- degrade improper folded proteins
- destroy aberrant proteins
- controls protein activity

56

What is the specificity that allows for proteasomes to bind?

two E1 ubiquitin enzymes and 1 proteasome

57

What is bortexomib?

powerful proteasome inhibitor

58

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

- cancer in plasma cells
- treated with proteasome inhibitors

59

In what ways can ubiquitin ligase be activated?

- phosphorylation by protein kinase
- allosteric transition by ligand binding
- allosteric transition by protein subunit addition

60

In what ways is a degradation signal activated?

- phosphorylation by protein kinase
- protein dissociation that unmasks a certain region
- creating a destabilizing N-terminus

61

What are the effects of glucocorticoid cortisol?

- response to stress
- raise BG
- aid with fat, protein, carb metabolism
- diurnal

62

When will glucocorticoid cortisol levels be high and low?

- high: 8 am
- low: midnight

63

What is the effect of methyl groups adding to DNA?

- DNA methylation leads to repressing gene expression

64

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

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

65

What is genomic Imprinting?

- differential expressio nof genetic material depending on the parent of origin

66

What is epigenetics?

- regulation of expression of gene activity without altering gene structure, such as methylation

67

What prader willi syndrome?

- caused by paternal deletion on chromosome 15

68

What is stage one of prader willi?

- infantile hypotonia
- poor suck
- feeding difficulties
- failure to thrive

69

What is stage two of prader willi?

- hyperphagia
- onset of early childhood obesity

70

What causes prader willi syndrome?

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