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Lec1HumanGeneTranscription Flashcards

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1
Q

What is POU1F1?

A

a transcription activator (transactivator) for GH, PRL and TSHs in ant pituitary gland

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2
Q

If POU1F1 is mutates, what occurs>

A

It leads to a decrease in GH, PRL, TSH (all hormones)

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3
Q

In the article related to pituitary hormone deficiency, the young patient had a severe decrease on GH, PRL, and TSH due to

A

heterozygous mutations (2 separate mutations on POU gene)

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4
Q

What are the heterozygous mutations that occurred for this pt?

A
  1. Deletion frameshift : deleted a base and it caused the reading frame to be different, so different amino acids) causing lacked DNA binding domain
  2. A missense mutation (diff protein) in the C-terminal
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5
Q

True or False RNA synthesis is transcription

A

True

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6
Q

What does every gene need for activation of transcription by RNA poly 2?

A
  1. every gene of ever cell has nonspecific proteins: to do PIC
  2. every gene of every cell has nonspecific elements: TATA seq,non specific DNA seq

nonspecific=every gene/cell has them

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7
Q

How is transcription activated the right time and right place?

A

every cell has SPECIFIC proteins/elements that allow for specific genes to be transcribed.

ex: liver cells has specific elements that create protein for specific liver function

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8
Q

_______ is the most efficient place to regulate

A

Transcription

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9
Q

RNA poly 2 transcribes

A

all protein-coding genes

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10
Q

RNA poly 1 transcribes

A

rRNA

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11
Q

All RNA polymerase has their own ____

A

PIC

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12
Q

RNA poly 2 has binding sites for ___ _____ which is why it is used for protein coding genes.

A

splicing factors

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13
Q

What is similar between RNA poly 1,2,3?

A

They all have their own PIC

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14
Q

TATA box is 4 NT. SSDBP recognizes 10 NT so we need to methylate H3K4. Why?

A

4NT is to small to recognizes to we methylate histone to create more binding sites to help recruit PIC

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15
Q

The TATA is too small for SSDNP to recognize so what do we do?

A

H3K4 methylation to help recruit PIC

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16
Q

What is TATA?

A

it is non specific and its present in almost all coding genes (10-20 bp upstream)

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17
Q

What is TFIIH?

A

It is non specific and has helicase activity and phosphorylates carboxyl end of RNA poly 2 (CTD) (HELICASE AND KINASE )

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18
Q

What is TFIID?

A

Contains a subunit that recognizes H3, K4 methlylation (post translational modification) AND has TBP to bind of TATA box (many subunit/polypeptide)

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19
Q

We need _____ nucleotide

A

triphosphate

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20
Q

What are some examples of non specific proteins, termed “general transcription factors” (GTFs)

A

TFIID, TFIIH, RNA poly 2

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21
Q

What binds to DNA?

A

Transactivators and TFIID (TBP specifically)

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22
Q

TF in TFIIX referes to

A

transciption factor

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23
Q

II in TFIIX refers to

A

RNA poly2

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24
Q

X in TFIIX refers to

A

any protein A-H

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25
Q

A kinase does what?

A

phosphorylates

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26
Q

What does TAF stand for?

A

TBP Associated Factors

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27
Q

The ____ subunit of TFIID recognizes _____ and binds the _____

A

TBP, H3K4, TATA

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28
Q

The ____ subunit of TFIID binds_____

A

TAF, other proteins

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29
Q

What represents the start of transcription?

A

TFIIH phosphorylates carboxy terminal domain of RNA poly2 (on serine 5)

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30
Q

What starts the PIC?

A

TFIID (TBP and TAF)

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31
Q

True or false TATA box is a specific DNA sequence at the start of every gene

A

FALSE (non specific DNA sequence) at the start of every gene

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32
Q

Most of the GTF’s assemble by interacting with

A

each other, NOT by contacting DNA

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33
Q

Transcription factors are the same as transactivators which are

A

proteins that activate transcription

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34
Q

What are the decoys?

A

TFIIF, TFIIE

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35
Q

Which subunit of TFIID recognizes the TATA box?

A

TBP

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36
Q

Which subunit of TFIID recognizes the other DNA sequences near the transcription start point, regulates DNA binding by TBP

A

TAF

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37
Q

Unwinds DNA at the transcription start point, phosphorylates Ser5 of the RNA poly CTD, releases RNA poly from the promoter, initiating RNA synthesis

A

TFIIH

38
Q

True or False TAFs DO NOT directly bind to DNA

A

true, its binding on to other proteins like transactivators

39
Q

TAFs provide what for transactivators?

A

binding sites

40
Q

What is so important about the interaction of transactivators with TAFs in TFIID?

A

Transactivators bind to TAF and stabilizes the weak interaction with DNA since TBP binds only the “TATA” seq

41
Q

What does RNA poly 2 do?

A

synthesizes RNA

42
Q

Regulation of eukaryotic (euk) transcription can be

A

developmental or inducible

43
Q

What is developmental regulation of euk transcription?

A

transcription of different genes in different tissues or at different developmental stages
1. Globin switching: biochemical change
2. heart morphology: morphological change

44
Q

What is inducible regulation of euk transcription?

A

Transcription of genes in response to a hormone. Specific pathways that activate transactivators and transcription occurs
1. TNF alpha
2. JAK/STAT
3.Hedgehog
4.RAS
5.FGF

45
Q

Eating isoflavones they will bind to receptor and your cells go into apoptosis. What type of regulation of eukaryotic transcription is this?

A

inducible regulation

46
Q

A person in infected with bacteria, and produce interferons. These binds to outside of lymphocytes and produce T cells and antibodies. What type of regulation of eukaryotic transcription is this?

A

Inducible regulation

47
Q

True or False Transactivators are just upstream

A

FALSE, transactivators can be up or down stream

48
Q

A basic element for SPECIFIC developmental and inducible regulation of transcription is that “genes” (can be subset or 1) contain __________ , which are short, specific sequences of DNA

A

regulatory (or response) elements (not present in other genes)

49
Q

A basic element for SPECIFIC developmental and inducible regulation of transcription is that the specific proteins that are able to bind _________ can activate or repress transcription. The proteins that activate transcription are referred to as ____

A

regulatory elements, transcriptional activators/transactivators

50
Q

A basic element for SPECIFIC developmental and inducible regulation of transcription is that the response elements are generally located _____ base pairs upstream or downstream of the TATA box

A

100-300

51
Q

A basic element for SPECIFIC developmental and inducible regulation of transcription is that a set of ______ contain similar response elements

A

genes regulated in concert

52
Q

Upon binding a sequence specific transactivator to the response elements it activates genes with

A

same or similar response element (does not need to be 100% identical)

53
Q

What is a polypeptide

A

specific exons spliced together, a transactivator

54
Q

True or False, transactivator binds to DNA + TFIID (specifically TAF protein) to help stabilize PIC

A

true

55
Q

What does this picture represent?

A

transactivator

56
Q

What are the structures of sequence specific transactivator?

A

amino terminal, c terminal, transactivation domain, DNA binding domain

57
Q

True or false, DNA binding domain is a regulatory element of DNA and binds specific DNA sequence

A

True

58
Q

The DNA binding domain can come _______ the transactivation domain in terms of which is on the N terminal or C terminal end

A

before or after (they can switch)

59
Q

Contacts other proteins especially TAFs and help TFIID be stable

A

Transactivation domain

60
Q

In consensus sequence___ DNA sequences are needed for response to interferon (it can vary). But certain nucleotides cannot vary if a particular transactivator is to bind a specific sequence

A

Similar

61
Q

True or false, transactivators have many binding sites which can be present at the same time (or not)

A

TRUE

62
Q

What does this picture represent?

A

Specific DNA sequences representing the binding sites for transactivators

In this photo we are looking for specific seq but it DOES NOT have to have a EXACT match, in b/w the specific seq it can be different

63
Q

The more transactivators you have the

A

greater the chance of transcription

64
Q

These wrap over and interact with general transcription factors and PIC to stabilize and help transcribe

A

co-activators and transcription regulators

65
Q

What do co-activators interact with and what do they recruit?

A

DNA binding proteins, HATs or contact the PIC

66
Q

Co-activators have the same role as transactivators but they dont bind a_______, but rather bind to a _____ that binds to the ____

A

DNA sequence, DNA protein, DNA sequence
(this is because it lacks a DNA binding domain that transactivators have)

67
Q

Co-repressors interact with what and mostly recruit what?

A

DNA binding proteins, HDAC

68
Q

Co-repressors do not bind

A

DNA

69
Q

What is an example of a classical co-repressor?

A

RB

70
Q

Transactivators typically bind where?

A

relatively close to the transcription start site

71
Q

Transactivators bind to which side of the transcription start site?

A

either side

72
Q

MYC and E2F1 E2F4 are example of what?

A

Transactivator

73
Q

What is MYC

A

human oncoprotein that increase proliferation

74
Q

Transactivators bind to their ____ regions, located among the regulatory elements of genes after being activated by a certain inducer or at a certain stage in tissue development

A

regulatory

75
Q

_______ recruit the TAFs of TFIID leading to the binding of the TFIID complex to the TATA box and brings RNA Poly 2 along.

A

Transactivators

76
Q

TFIID binding to the TATA box leads to the formation of the complete PIC and_______

A

transcription

77
Q

What three factors stabilize the PIC

A

Transactivator—-TAF interaction
TATA—-TBP binding
Histone post-translation modification (methylation of histone 3)

78
Q

What are 6 biochemical mechanisms that make transactivators available (activate transactivators)?

A
  1. Activate protein synthesis of transactivators
  2. Covalent modification: phosphorylate transactivators and activate it
  3. Add 2 subunits (EACH 4-5 BP) and combine them to activate
  4. Remove inhibitor on transactivator and now activate
  5. Stimulation of nuclear entry
  6. Release transactivator from membrane now its active
79
Q

In the reading about melanoma, many oncogens in melanoma effect the

A

RAF/MEK/ERK (MAPK) pathway

80
Q

Most melanomas have activating mutations in _____ that exerts an oncogenic effect by activating ____ pathway increasing proliferation and survival (aka cancer)

A

BRAF (V600 E mutation that turns valine into glutamate), MAPK

81
Q

____ have worked for melanoma treatment but there’s resistance

A

BRAF inhibitors

82
Q

MAPK signaling axis

A

Extracellular (Growth factor)
RAS
MAP3K (MAPK kinase kinase) —>RAF
MAP2K (kinase)—>MEK
MAPK—>ERK
Phosphorylate Transcription factors

83
Q

The ERK pathway is constantly active in up to ___% of melanomas, and increase with early to advanced stages

A

90%

84
Q

N-RAS mutation observed _____% of melanomas (which activates ERK)

A

15/30%

85
Q

What is the name of PLX4032 and what does it do?

A

VEMURAFENIB: this is a potent/selective BRAF inhibitor
10x more selective for v600E
no activity with other kinases

86
Q

What is the mechanism of resistance of VEMURAFENIB?

A
  1. upregulate proteins to incr ERK
  2. platelet derived growth factor receptor B mediates activation of alternative survival pathway
  3. no gate keeper mutation (prevents binding to target site)
87
Q

True or False Transactivators only bind upstream to the transcription start site
a. True
b. False

A

false

88
Q

Which of the following proteins below has both helicase and kinase activity?
a. TFIIA
b. TFIIE
c. TFIID
d. TFIIH

A

d

89
Q

Explain the need for Histone methylation to initiate transcription
a. The TATA box only has 6 base pairs and SSDBP’s can only recognize 15 base pairs
therefore histone methylation is needed
b. The TATA sequence is significant enough for transactivators to recognize and histone
methylation is not needed
c. The TATA sequence only has 4 base pairs, and 10 base pairs are required for SSDBP’s
to recognize the sequence
d. The TATA sequence is located at the transcriptional start site therefore histone

A

c

90
Q

What is indicated in the arrow below ? (black arrow, bottom right corner)
A) Transactivator
B) Histone
C) Specific transcription factor
D) Co activator

A

b

91
Q

Which of the following can directly bind to DNA?
a. Co activators
b. Co repressors
c. Transactivators
d. TFIID
e. C and D

A

e

Genetics (12 decks)

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