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Human Molecular B > Lecture 8/9 -control Of Gene Expression Pt II > Flashcards

Lecture 8/9 -control Of Gene Expression Pt II Flashcards

1
Q

What is the mechanism for transcriptional Activation by activator proteins?

A
  1. Activation by recruitment.

2. Activation by conformational change. 3. Activation by altering chromatin structure.

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2
Q

Activation by recruitment

A

Activation domain interacts with one or more components Of transcriptional machinery and stabilises its binding to template DNA

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3
Q

Activation by conformational change

A

Activation domain induces a conformational change in a component of the basal transcriptional machinery to stimulate RNA polymerase II to initiate transcription

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4
Q

Activation by altering chromatin structure

A

Activation domain recruits chromatin remodelling/modifying proteins (co-activators) to modulate chromatin structure around promoters

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5
Q

What are the transcriptional factor activation domains?

A

Acidic region.

Glutamate rich regions Proline rich regions

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6
Q

What factors contains acidic regions?

A

Yeast GCN4 GAL4.
Nuclear receptors

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7
Q

What factors contains Glutamate-rich regions?

A

SP1, Oct1,Oct2, AP2

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8
Q

Which factors contain proline rich regions ?

A

CTF/NF1 AP2 c-jun Oct2

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9
Q

What are the other roles of activation by recruitment?

A

Increases binding of a particular component of the basal machinery so enhancing its assembly Activator alters confirmation of an already bound factor so stimulating the activity/or stability of the complex

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10
Q

Activators can interact with TFIID

A

Enhances binding of TFIID to TATA box, improving rate of PIC complex Alter the confirmation of TFIID stimulating its activity by increasing its ability to recruit other PIC components or by enhancing ability to stimulate transcription.
Interaction is through TBP or one or more of TAFs

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11
Q

Activators can interact with TFIID via TAFs

A

Different activators target different TAFs.

Different cell types can have cell type-specific TAFs

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12
Q

What are TAFs a critical intermediary of?

A

Between activators and basal transcription complex

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13
Q

Activators can interact with TFIIB

A

Stimulation of assembly of PIC/activity of basal transcriptional complex after TFIID has bound

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14
Q

Who do TFIIB interact with ?

A

Acidic activators

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15
Q

What do CTD of RNA pol II interact with?

A

Mediator complex

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16
Q

Why is the interaction between CTD and mediator important?

A

Required for the response to transcriptional activators

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17
Q

What do mediator form?

A

molecular bridge between activators and RNA pol II

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18
Q

How many subunits does the mediator complex have?

A

30’subunit

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19
Q

How many sub complexes does the mediator complex have?

A

3

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20
Q

What are the three sub complexes of mediator complex?

A

Head, middle and Tail

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21
Q

What does the head of the mediator complex interact with?

A

RNA pol II CTD

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22
Q

What does the tail of the mediator complex interact with?

A

Activators

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23
Q

What do different classes of activators interact with ?

A

Different mediator subunits

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24
Q

Mediator interacts with activator proteins and what else?

A

Pol II transcription machinery

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25
Q

What is the principle that governs the function of all activators?

A

DNA binding domain determines specified for the target promoter enhancer

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26
Q

What is the DNA binding domain responsible for?

A

Localising a transcription-activating domain in the proximity of the basal apparatus

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27
Q

What is the structure of an Activator that works directly?

A

DNA binding domain and an activating domain within same protein that affects transcription directly

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28
Q

What happens when an Activator does not have an activating domain?

A

Work by binding a co-Activator that has activating domain (interaction between 2 distinct proteins)

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29
Q

What does co-Activator do?

A

Does not bind DNA itself Interacts with a DNA-bound transcriptional activator to transmit the signal to the basal transcription complex

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30
Q

What is an example of co-Activator?

A

CREB-binding protein (CBP/p300) which is recruited to DNA by the DNA-binding transcription factor partner, CREB

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31
Q

What does CREB-binding protein (CBP/p300) mediate?

A

Transcriptional activation via a number of other DNA-binding transcription factors partners involved in a variety of signalling pathways

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32
Q

What is CREB-binding protein (CBP)?

A

Histone Lysine acetyltransferase

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33
Q

What acts upon CBP/p300?

A

CREB.
Steroid/thyroid hormone receptors STATs NF-KB
AP1.
SREBP MyoD P53

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34
Q

CREB

A

Cyclic AMP

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35
Q

Steroid/thyroid hormone receptors

A

Steroid/thyroid hormone

36
Q

STATs

A

Interferon/cytokines

37
Q

NF-KB

A

Inflammation

38
Q

AP1

A

Growth stimulation

39
Q

SREBP

A

Cholesterol

40
Q

MyoD

A

Muscle differentiation

41
Q

P53

A

Growth arrest

42
Q

Histone Lysine acetyltransferase

A

Recruited by a variety of separate DNA-binding partners (activators) to activate transcription Mediate transcriptional activation by changing chromatin structure directly (charge) or indirectly (recruitment of acetyl-Lysine binding proteins) Allows access fo DNA and transcriptional start sites by opening up chromatin

43
Q

What is Lysine (K) acetyltransferase (KAT)?

A

Enzyme present in large complexes that acetylates Lysine residues in histonnes

44
Q

Where are HAT recruited to?

A

Recruited to promoters as co-activators by transcriptional activators Activator transcription from promoter; opening up/loosening chromatin is by recruitment of basal transcriptional machinery

45
Q

What is GCN4?

A

Transcriptional activator that binds to upstream activating sequence (UAS) though DNA-binding domain

46
Q

What does GCN4 activation domain interact with?

A

Multi-protein GCN5 HAT complex (co-Activator)

47
Q

What does GCN4 allow?

A

Access of PIC to DNA and transcriptional start site

48
Q

Transcriptional effect of acetylation of Lysine

A

Activation

49
Q

Transcriptional effect of methylation is Lysine at H3; 4,36 and 79

A

Activation

50
Q

Transcriptional effect of methylation of Lysine at H3;9,27 and H4 position 12,20

A

Repression

51
Q

Transcriptional effect of methylation at arginine

A

Activation

52
Q

transcriptional effect of ubiquilated Lysine at H2B position 120

A

Activation

53
Q

Transcriptional effect of ubiquilated Lysine at H2A position 119

A

Repression

54
Q

Transcriptional effect of sumoylated Lysine

A

Repression

55
Q

transcriptional effect of phosphorylated serine/threonine

A

Activation

56
Q

What recognises acetyl lysines?

A

A family of binding proteins containing bromodomains

57
Q

TAFII250

A

Part of TFIID and therefore transcription is promoted by recruitment of the PIC

58
Q

What can remodel chromatin?

A

Transcriptional activators

59
Q

What can acetylation of histones do?

A

Weakens/loosens nucleosome which can: Facilitate access of an Activator to DNA Recruitment of activators tang recognise and bind to acetyl-Lysine
Promote nucleosome displacement from promoter in an energy-dependent process

60
Q

What is chromatin remodelling?

A

The energy-displacement or re-organisation of nucleosomes that occurs in conjugation with activation of genes for transcription

61
Q

What does all remodelling complexes contain?

A

Related ATPase catalytic subunit

62
Q

What can remodelling complexes do?

A

Alter, slide or displace nucleosomes

63
Q

What can some remodelling complexes exchange?

A

One Histone for another in a nucleosome

64
Q

What does transcriptional activation involve?

A

Multiple changes to chromatin

65
Q

What is transcriptional activation?

A

Synergistic

66
Q

What are the mechanisms of action of Transcriptional Repressors?

A

Prevent an Activator binding through chromatin structure Overlapping binding sites Repressor sequesters the Activator Repressor quenches the transcriptional Activation ability of the Activator Repressor degrades Activator Directly Repress transcription

67
Q

Transcriptional Repression through chromatin structure

A

Establish repressive/tightly packed chromatin (heterochromatin) around proteins

68
Q

What is Histone deacetylase (HDAC)?

A

Enzyme that removes acetyl groups from histones; May be associated with repressors of transcription

69
Q

Where are deacetylases present?

A

Complexes with repressor activity

70
Q

What can Repressors interact with?

A

Co-Repressors

71
Q

What is UME6?

A

Transcriptional repressor that binds to upstream repressor sequence (URS1)

72
Q

What does UME6 interact with?

A

Separate multi-protein SIN3 complex that includes RPD3 Histone deacetylase

73
Q

What is Methylation catalysed by?

A

Histone methyltransferase (KMTs)

74
Q

Readers of Lysine methylation

A

Methyl-lysines are recognised by a family of binding proteins containing chromodomain

75
Q

HP1

A

Heterochromatin assembly Transcriptional silencing

76
Q

Where does HP1 bind to?

A

Methyl-Lysine on Histone H3 Lysine 9 through its chromodomain

77
Q

During early embryogenesis what do Repressors associate with?

A

PRC2 co-repressor complex

78
Q

What does PRC1 complex bind to?

A

Methylated Lysine 27 and further condenses chromatin into inactive form

79
Q

How is Repression maintained?

A

Absence of the original repressor throughout adult development - transcriptional memory

80
Q

What do Lysine methylation and acetylation do?

A

Cross talk e.g. H3K9

81
Q

What can Lysine be?

A

acetylated or methylated

82
Q

How can processes such as transcription be regulated?

A

Switching modifications

83
Q

What do Repressor bind to?

A

specific DNA sequence preventing/blocking the action of the Activator (A)

84
Q

What is a repressor which ubiquitinate the P53 Activator and promote degradation by proteases?

A

MDM2

85
Q

What is a repressor that is itself a protease and degrades the Activator directly ?

A

AEBP1

86
Q

What is Dr1 factor?

A

bind TBP preventing binding of TFIIB and therefore assembly of the PIC

87
Q

What displaces TBP from DNA?

A

Mot1

Human Molecular B (13 decks)

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