Chapter 9: Regulation of Transcription Flashcards

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1
Q

key to providing the cell with the correct amount of gene product at the correct time

A

transcriptional regulation

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2
Q

transcriptional regulation underlies () and employs a wide range of mechanisms

A

cell differentiation and development

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3
Q

one level of transcriptional regulation is (1), but most regulation comes from (2)

A
  1. promoter strength
  2. targeted gene regulation
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4
Q

targeted gene regulation can happen at (3)

A
  1. transcription initiation (most prevalent)
  2. elongation or termination
  3. regulation from transcribed RNA itself
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5
Q

regulatory (1) regulate transcription by binding to regulatory (2)

A
  1. proteins
  2. sequences
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6
Q

control relative amount of transcription from promoter

A

regulatory proteins

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7
Q

2 types of regulatory proteins

A
  1. repressors - decrease transcription level
  2. activators - increase transcription level
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8
Q

specific DNA regions to which regulatory proteins bind

A

regulatory sequences

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9
Q

in bacteria, sequences recognized by regulatory proteins are called ()

A

operator sites

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10
Q

bacterial operator sites are typically ()

A

close to or overlap promoter

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11
Q

if operators or (and common for enhancers) are distal to the gene, DNA must loop around for the regulatory protein to interact with the polymerase, sometimes aided by ()

A

architectural DNA binding proteins

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12
Q

eukaryotic analogs to bacterial operator sites; usual distal (1000s of bps away) from genes

A

enhancers

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13
Q

to increase the sophistication and subtlety of regulation, eukaryotic regulatory sequences frequently bind ()

A

several regulatory proteins

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14
Q

found in more complex eukaryotes; have a combination of enhancer and insulator elements

A

locus control regions (LCRs)

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15
Q

blocks unwanted interaction between enhancers and certain genes

A

insulators

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16
Q

role of LCRs in the expression of beta-globin genes

A

LCRs make sure that only fetal Hb is expressed while in the womb, and only adult Hb is expressed outside of the womb

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17
Q

each regulatory protein has a () that recognizes a specific sequence

A

DNA binding domain

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18
Q

regulatory proteins are often (), allowing them to have additional domains that give them additional functions

A

modular

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19
Q

transcription level changes in response to (1); this can be done by changing the (2) of the regulatory proteins

A
  1. changing conditions
  2. activity
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20
Q

small molecules that can bind directly to regulatory proteins and change their conformation upon binding

A

allosteric effectors

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21
Q

() can also change how regulatory proteins interact

A

phosphorylation or other covalent modifications

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22
Q

covalent modification, along with other factors such as () serve to fine-tune regulation of gene expression

A

regulator abundance and localization

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23
Q

() chromatin tends to be actively transcribed

A

hyperacetylated

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24
Q

hypoacetylated chromatin tends to have () levels of transcription

A

low

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25
Q

other histone modifications like (4) also affect transcription, but the relationship is not yet clear

A
  1. methylation
  2. phosphorylation
  3. ubiquitination
  4. sumoylation
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26
Q

a () has been proposed (and is being actively researched) in which certain combinations of modifications would lead to specific outcomes

A

histone code

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27
Q

() are tailored to fit DNA; some are found throughout life, other are found just in eukaryotes or metazoans

A

DNA-binding motifs

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28
Q

the () is a common DNA-binding motif and is found in many protein folds

A

helix-turn-helix

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29
Q

the second helix in the helix-turn-helix motif is called the (), and fits into the major groove of DNA

A

recognition helix

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30
Q

recognition helices in helix-turn-helix motifs read the DNA sequence through ()

A

interactions with the base pairs

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31
Q

many helix-turn-helix DNA-binding motifs are dimers, with the recognition helices spaces () apart to fit in neighboring grooves

A

3.4 nm

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32
Q

the () is a monomeric helix-turn-helix, commonly found in eukaryotes; its recognition helix is longer than its bacterial counterparts

A

homeodomain

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33
Q

the sidechains of homeodomain motifs interact with (1), while its N-terminal arm makes contacts in the (2)

A
  1. DNA base pairs
  2. minor groove
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34
Q

a prominent part of many DNA binding folds -> most common DNA-binding domain in the human genome; has a domain of ~30 amino acids

A

zinc finger

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35
Q

structure of a zinc finger

A

alpha helix and 2 beta strands around a central zinc ion

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36
Q

the zinc ion in zinc fingers interacts with (); these are always conserved in proteins with zinc fingers

A

2 cysteines and 2 histidines -> Cys2His2 zinc fingers

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37
Q

each zinc finger inserts its alpha helix into the (1) of DNA and recognizes (2)

A
  1. major groove
  2. 2-3 base pairs
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38
Q

how do proteins with zinc fingers enhance specificity when recognizing DNA sequences

A

proteins have multiple zinc fingers -> zinc fingers are multimerized

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39
Q

alpha helices that wind around each other; form part of some DNA-binding domains

A

coiled-coils

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40
Q

2 main examples of coiled-coil motifs in DNA-binding domains

A
  1. basic region-leucine zipper (bZIP) proteins
  2. basic region-helix-loop-helix (bHLH) proteins
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41
Q

structure of bZIP proteins

A
  • 2 alpha helices about 60 AAs long
  • helices have hydrophobic leucine residues
  • helices splay and sit in the DNA major groove at the N terminal end
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42
Q

structure of bHLH proteins

A
  • 4 helices joined by a loop (four-helix bundle)
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43
Q

both bZIP and bHLH proteins become () when not bound to DNA

A

unstructured

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44
Q

the () binds DNA with 2 beta strands

A

MetJ repressor

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45
Q

(1), part of the mammalian transcriptional regulator nuclear factor (2), are largely beta sheets

A
  1. p50 and p65
  2. NF-kappa(B)
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46
Q

() are entirely made up of beta sheets and connecting loops

A

immunoglobulins

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47
Q

a simple way to regulate transcription is to ()

A

prevent RNA pol from accessing the promoter

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48
Q

bacterial genes that are located, regulated, and transcribed together

A

operon

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49
Q

the () is a protein with a helix-turn-helix DNA-binding motif that responds to the level of tryptophan in the cell

A

Trp repressor

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50
Q

when tryptophan levels are high in the cell, Trp repressor binds to () and blocks RNA pol from binding

A

Trp operator

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51
Q

Trp repressor can only bind to DNA when (1), which only happens when (2)

A
  1. it is bound to Trp
  2. Trp levels are high
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52
Q

regulatory protein that enhances the binding of RNA pol to a promoter to increase transcription levels

A

activators

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53
Q

() activates more than 100 E. coli promoters when carbon sources are low

A

catabolite activator protein (CAP)

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54
Q

the catabolite activator protein (CAP) is also called

A

cAMP receptor protein (CRP)

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55
Q

() leads to increase in cAMP levels -> cAMP binds to CAP and increases CAP’s binding to DNA

A

glucose depletion

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56
Q

CAP enhances RNA pol binding to DNA by binding to the ()

A

CTD

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57
Q

2 classes of promoters that interact with CAP

A
  1. class I - CAP binds upstream of promoter
  2. class II - CAP binding site overlaps the RNA pol binding site
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58
Q

() responds to low glucose levels in the cell by allowing the cell to metabolize lactose instead (if lactose is present) -> contains genes that are needed for metabolizing lactose

A

lac operon

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59
Q

(1) and (2) regulate the lac operon

A
  1. CAP
  2. LacI repressor
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60
Q

how does the LacI repressor regulate the lac operon

A
  1. when lactose is present, it binds to the LacI repressor and prevents it from binding to operator
  2. when lactose is absent, LacI is able to bind to lac opertor to prevent transcription of lac operon
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61
Q

how does CAP activator regulate the lac operon

A
  1. glucose present: decreased cAMP levels -> cAMP doesn’t bind to CAP and CAP doesn’t bind to lac operator
  2. glucose absent: increased cAMP levels -> cAMP binds CAP and CAP binds to lac operator to increase transcription of lac operon
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62
Q

in () conditions, transcription for lac operon is strongly on

A

low glucose, available lactose

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63
Q

in (1) conditions, there is weak transcription of lac operon; aka (2)

A
  1. high glucose, available lactose
  2. basal transcription
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64
Q

if the spacing between -10 and -35 promoter elements is (), RNA pol binding is weakened -> another layer of regulation

A

very large

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65
Q

() can change the way promoter elements are spatially related to each other, thereby enhancing transcription

A

MerR family regulators

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66
Q

the MerR protein can bind to the DNA and change its conformation to ()

A

a spacing more favorable for RNA pol binding

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67
Q

RNA pol holoenzyme that contains sigma 54 needs to be activated by () to drive promoter opening

A

ATP hydrolysis

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68
Q

() is an example of an activator with sigma 54

A

NtrC

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69
Q

NtrC binds at enhancer elements and activates transcription when ()

A

phosphorylated

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70
Q

phosphorylation triggers () of NtrC, and promotes its interaction with the polymerase at the promoter

A

oligomerization

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71
Q

in NtrC activation, oligomerization stimulates NtrC’s (), which helps promote the formation of the open complex

A

rate of ATP hydrolysis

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72
Q

responses to external signals often involve () that leads to a signaling cascade

A

phosphorylation of a receptor protein

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73
Q

a 2-component signal transduction pathway is an example of how phosphorylation of a receptor protein leads to a ()

A

signaling cascade

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74
Q

2-component signal transduction pathway have a (1) and a (2)

A
  1. sensor kinase
  2. response regulator
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75
Q

the sensor kinase in a 2 component transduction pathway has a () that becomes autophosphorylated on receipt of the signal

A

histidine (histidine kinases)

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76
Q

in 2 component transduction pathways, the phosphoryl group on an autophosphorylated histidine is transferred to an (1) in a (2)

A
  1. aspartic acid residue
  2. response regulator protein
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77
Q

Complex and differing signals regulate transcription. The outcome of the combination of signals, which can be (1), depends on the (2)

A
  1. antagonistic
  2. strength of the opposing regulators.
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78
Q

() infects E. coli by injecting its chromosome into the
bacterium

A

Bacteriophage lambda

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79
Q

after infecting E. coli, bacteriophage lambda enters either (1) or (2)

A
  1. lytic growth
  2. lysogeny
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80
Q

when bacteriophage lambda infect E. coli, () produces lots of copies of the virus in the bacterial cell and eventually leads to cell lysis

A

lytic growth

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81
Q

lytic growth allows a phage to () a cell that may not survive

A

escape

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82
Q

when bacteriophage lambda infects E. coli, () happens when the virus integrates into the host genome and becomes dormant

A

lysogeny

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83
Q

in lysogeny, the integrated virus is called a ()

A

prophage

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84
Q

lysogeny allows bacteriophage lambda to multiply in conditions where ()

A

there might not be enough nearby cells to infect

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85
Q

when E. coli containing prophage endures (1), the phage can be triggered to excise itself and (2)

A
  1. difficult conditions (e.g. DNA damage)
  2. undergo lytic growth
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86
Q

lysis and lysogeny are regulated by levels of the DNA-binding proteins (3)

A
  1. cI (lambda repressor)
  2. cII
  3. Cro
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87
Q

cI, cII, and Cro bind to sites in the phage chromosome and control transcription at the ff 4 promoters:

A
  1. P_R
  2. P_L
  3. P_RE
  4. P_RM
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88
Q

(2) are the early promoters involved in the choice between lysis and lysogeny -> host RNA pol initiates basal transcription

A

P_R and P_L

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89
Q

P_R promoter encodes (1) regulators, while P_L encodes (2)

A
  1. Cro and cII
  2. N protein
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90
Q

() prevents premature termination of the P_R transcript and thereby allows transcription of Cro and cII

A

N protein

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91
Q

if sufficient cII accumulates, it stimulates transcription at (1), which produces (2)

A
  1. P_RE
  2. cI
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92
Q

cI stimulates (), which makes more cI

A

P_RM

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93
Q

high cI levels result in cI binding to P_R and P_L promoters -> repress (1) and activates transcription of (2)

A
  1. lytic genes
  2. integrase
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94
Q

() promote and maintain lysogeny

A

high cI levels

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95
Q

if not enough cII is produced, (1) binds to P_RM and represses (2)

A
  1. Cro
  2. cI production
96
Q

by preventing (), Cro ensures the expression of lytic genes from P_R and P_L

A

cI synthesis

97
Q

(1) regulate the levels of cII -> cII is sensitive to host cell (2)

A
  1. environmental factors
  2. proteases
98
Q

if proteases are (), cII is degraded -> cI cannot accumulate and virus enters (2)

A
  1. highly active
  2. lytic growth
99
Q

the () of cI and Cro at 6 DNA-binding sites determine the choice between lysogeny and lysis

A

binding affinities

100
Q

cI has 2 domains that can form (1) and (2)

A
  1. tetramers
  2. oligomers
101
Q

Cro has a single small domain that binds as a ()

A

dimer

102
Q

operators O_L and O_R (for promoters P_L and P_R, respectively) each have () that cI or Cro can bind to

A

3 sites

103
Q

cI binds first to operators (), where it has strongest affinity

A

OL1 and OR1

104
Q

binding of cI to OL1 and OR1 recruis another cI to weaker sites ()

A

OL2 and OR2

105
Q

the cI units bound to operators OL1-2, OR1-2 (1) to form a (2)

A
  1. oligomerize
  2. looped-out structure
106
Q

oligomerization of the cI units at operator sites stops (1) and promotes (2) -> increase in cI levels

A
  1. RNA pol binding to PL and PR
  2. transcription from PRM
107
Q

with increasing levels of cI, cI binds to (), stoping the activation of PRM -> suppressing cI synthesis

A

OL3 and OR3

108
Q

binding of cI to OL3 and OR3 serves as ()

A

autoregulation

109
Q

if there is insufficient cI, Cro accumulates and binds with the greatest affinity to (), blocking PRM and suppressing cI synthesis

A

OR3

110
Q

more Cro synthesis leads to binding at the other (1), autoregulating Cro by preventing RNA pol binding to (2)

A
  1. OR and OL sites
  2. PR promoter
111
Q

the prophage must be able to excise itself and switch from lysogeny to lytic growth if the host cell is ()

A

threatened

112
Q

excision of prophage is brought about by a response to () that disables cI

A

DNA damage

113
Q

DNA damage in a bacteriophage infected bacterium prompts a (1), activating (2)

A
  1. host SOS response
  2. RecA
114
Q

cleaves cI so it cannot dimerize or cooperate with other cI units

A

RecA

115
Q

after cI cleavage by RecA, cI dissociates from (), allowing transcription from PL and PR-> allowing lytic growth

A

operator sites

116
Q

regulation can also occur at the () steps of transcript synthesis

A

elongation and termination

117
Q

some phage lambda genes are transcribed only when transcription termination is actively prevented -> this is called ()

A

anti-termination

118
Q

() prevent stalling and termination by altering the properties of bacterial RNA pol

A

bacteriophage lambda N and Q proteins

119
Q

initially, transcription from PL and PR promoters successfully makes Cro and N protein until RNA pol encounters termination sites ()

A

tL and tR

120
Q

when N protein builds up, it stops ()

A

termination of transcription from PL and PR promoters

121
Q

N proteins bind to (1) in the transcribed RNA in a (2)

A
  1. nut sites
  2. step-loop form
122
Q

when N protein binds to nut sites, it allows several proteins to be (), allowing RNA pol to transcribe through tL and tR

A

recruited and interact with RNA pol

123
Q

with termination at tL and tR suppressed (due to build up of N proteins), downstream genes can be transcribed, including ()

A

bacteriophage lambda protein Q

124
Q

() overrides termination at the PR promoter, allowing transcription of late lytic genes

A

Q protein

125
Q

in contrast to N protein, Q prevents termination by ()

A

binding directly to DNA

126
Q

the Q binding site (QBE) is between the () of the PR promoter

A

-35 and -10 elements

127
Q

without Q protein, transcription terminates very early, just downstream of ()

A

-10

128
Q

Q protein directly contacts the (1) and allows elongation to resume; Q remains associated with the (2)

A
  1. sigma subunit (sigma70)
  2. elongation complex
129
Q

() controls bacterial genes needed for amino acid biosynthesis

A

attenuation

130
Q

attenuation exploits ()

A

folding of RNA into alternative secondary structures

131
Q

the trp operon is controlled by Trp levels in the cells -> different levels cause the transcript to have ()

A

different secondary structures

132
Q

the genes for Trp synthesis are transcribed together -> a ()

A

polycistronic message

133
Q

the mRNA for Trp synthesis has a leader sequence near the start that has an (1) and 2 sequences that can form (2)

A
  1. intrinsic terminator; an attenuator
  2. stem-loops
134
Q

the leader sequence in mRNA for Trp synthesis has a () with lots of codons for Trp

A

small open reading frame

135
Q

the leader sequence in mRNA for Trp synthesis has 4 blocks that can form alternative pairing arrangements: 1 + 2

A

stem-loop

136
Q

the leader sequence in mRNA for Trp synthesis has 4 blocks that can form alternative pairing arrangements: 3 + 4

A

Rho-independent terminator

137
Q

the leader sequence in mRNA for Trp synthesis has 4 blocks that can form alternative pairing arrangements: 2 + 3 (1 and 4 are unpaired)

A

stem-loop

138
Q

in low Trp conditions, ribosome stalls while translating the peptide from leader sequence of mRNA (for Trp synthesis) -> region 1 is (a), region 2 and 3 (b), preventing 3 and 4 from (c), so transcription continues

A

a. blocked
b. form a stem-loop
c. binding and forming a terminator

139
Q

() are portions of a transcript that can directly bind a small molecule that controls the RNA secondary structure -> regulates transcription or translation

A

riboswitches

140
Q

riboswitches have 2 regions:

A
  1. aptamer - binds to metabolite
  2. expression platform - controls transcription or translation
141
Q

the () regulates adenine synthesis and transport -> gene expression depends on whether a terminator or anti-terminator forms

A

B. subtilis adenine riboswitch

142
Q

what happens to B. subtilis adenine riboswitch in low adenine conditions

A

regions 2 and 3 form anti-terminator -> transcription proceeds

143
Q

what happens to B. subtilis adenine riboswitch in high adenine conditions

A

regions 3 and 4 form a terminator

144
Q

Eukaryotes typically regulate transcription via DNA-binding proteins that recruit (1) or (2)

A
  1. co-activators
  2. co-repressors
145
Q

example of eukaryotic DNA-binding protein that recruits co-activator/co-repressor

A

ELK1, which recruits Mediator

146
Q

extracellular signals that promote entry into mitosis

A

mitogens

147
Q

in the absence of mitogens, ELK1 binds to () but doesn’t activate transcription

A

serum response factor (SRF)

148
Q

Mitogen binding at the cell surface activates kinases, which ()

A

phosphorylate ELK1

149
Q

phosphorylated ELK1 recruits (), promoting transcription

A

mediator

150
Q

() regulates genes that are responsible for galactose metabolism

A

Gal4

151
Q

Gal4 dimer activates transcription by binding to the ()

A

UASG sequence

152
Q

Gal4 activity is regulated by (), which respond to galactose in the cell

A

Gal80 and Gal3

153
Q

Unlike bacterial Trp repressor and CAP activator, the effector (galactose) for Gal80 and Gal3 doesn’t ()

A

bind directly to Gal4.

154
Q

in the absence of galactose, () binds to activating domain of Gal4, preventing transcription

A

Gal80

155
Q

in the absence of galactose, Gal80 is found in (1), while Gal3 is found in (2)

A
  1. nucleus and cytoplasm
  2. cytoplasm only
156
Q

in presence of galactose, galactose binds to (1), which allows (1) to bind to (2)

A
  1. Gal3
  2. Gal80
157
Q

in presence of galactose, Gal3 sequesters Gal80 in the ()

A

cytoplasm

158
Q

with Gal80 sequestered in the cytoplasm, Gal4 is able to recruit () and Mediator, which activates transcription

A

SAGA (co-activator complex)

159
Q

() responds to nutritional cues in yeast and can activate or repress transcription

A

Ume6

160
Q

where there is enough (1) in the cell, Ume6 binds DNA and recruits co-repressors (2)

A
  1. Nitrogen and Carbon
  2. Sin3, Rpd3, Isw2
161
Q

(): a histone deacetylase – histone deacetylation promotes more compact chromatin, which represses transcription

A

Rpd3

162
Q

(): a nucleosome remodeling enzyme, which helps establish the altered chromatin pattern

A

Isw2

163
Q

Ume6 is (1) in the absence of N and C, (2) dissociate

A
  1. phosphorylated
  2. Sin3 and Rpd3
164
Q

additionally, in the absence of N and C, a co-activator, () is recruited

A

Ime1

165
Q

() is involved in protecting the cell during abnormally high temperatures (heat shock) -> particularly observed in Drosophila

A

Hsp70

166
Q

promoter proximal pausing is used to prime Hsp70 (heat shock protein 70) for rapid transcription in response to ()

A

heat shock

167
Q

without heat shock at 25C, () binds upstream of hsp70

A

GAGA factor

168
Q

without heat shock at 25C, GAGA factor recruits (), which keeps the promoter free of nucleosomes and allows polymerase binding

A

NURF

169
Q

But RNA Pol is paused by negative elongation factors () -> polymerase complex is not phosphorylated enough

A

NELF, DSIF

170
Q

in transcription of Hsp70, without heat shock, Hsf monomers are present in the cell but ()

A

cannot bind to DNA

171
Q

with heat shock at 37C, Heat-Shock Factor (Hsf) trimerizes and binds to ()

A

heat shock elements (HSEs)

172
Q

when bound to HSEs, Hsf recruits Mediator and ()

A

p-TEFb (kinase)

173
Q

recruitment of Mediator and p-TEFb by Hsf () Pol Rpb1, NELF, DSIF -> resumes elongation

A

phosphorylates

174
Q

() also depends on anti-termination (similar to phage lambda N protein)

A

HIV transcription

175
Q

in HIV transcription, the (1) forms a step-loop called the (2) -> leads to transcription termination

A
  1. tar site
  2. TAR element
176
Q

in HIV transcription, transcription termination occurs if () is absent

A

Tat protein

177
Q

() binds to tar site in HIV transcription along with a cellular kinase -> phosphoryltates RNA pol II CTD -> relieves pausing and precents premature transcript termination

A

Tat (viral protein)

178
Q
  • regulation of a single gene with several different proteins, each of which is controlled by a different parameter
A

combinatorial control

179
Q

combinatorial control is the response of a gene to ()

A

multiple signals and regulatory proteins

180
Q

yeast cell type is controlled by () transcriptional factors

A

four

181
Q

yeast cell has 3 cell types:

A
  1. a
  2. alpha
  3. a/alpha
182
Q

() yeast cell types are haploid

A

a and alpha

183
Q

(1) type yeast cells are diploid and result from mating of (2)

A
  1. a/alpha
  2. a and alpha
184
Q

a/alpha yeast cells cannot mate, but can () when starved

A

undergo meiosis

185
Q

a. alpha, and a/alpha yeast cells have distinctive gene expression patterns, regulated by 4 proteins:

A

a1, alpha1, alpha2, and MCM1

186
Q

regulatory proteins for yeast cells: repressors

A

a1 and alpha2

187
Q

regulatory proteins for yeast cells: activators

A

alpha1, MCM1

188
Q

in yeast cells, a1, alpha1, and alpha2 proteins are encoded at the (1) on (2)

A
  1. MAT locus
  2. chromosome III
189
Q

in yeast cells, the MAT loci are different in different cell types:
1. a cells encode: (a)
2. alpha cells encode (b)
3. all 3 types encode (c)

A

a. a1
b. alpha1/2
c. MCM1

190
Q

in a-type yeast cells, MCM1 activates (1), while (2) are off

A
  1. a-specific genes
  2. alpha-specific
191
Q

in alpha-type yeast cells, (1) activates alpha-specific genes; (2) represses a-specific genes

A
  1. alpha1-MCM1
  2. alpha2-MCM1
192
Q

in alpha yeast cells, MCM1 activates transcription when bound by (1), and represses transcription when bound to (2)

A
  1. alpha1
  2. alpha2
193
Q

in a/alpha yeast cells, (1) form a heterodimer and repress haploid-specific genes: (2)

A
  1. a1-alpha2
  2. alpha1 and RME1
194
Q

() represses meiosis genes in yeasts; if this is no longer expressed, meiosis can occur

A

RME1

195
Q

Several proteins regulate (). This is important in viral defense by inhibiting synthesis of viral genome and stimulating host immune response)

A

human interferon-β

196
Q

A number of proteins bind to the interferon-β enhancer to form an ()

A

enhanceosome

197
Q

() between neighboring proteins are required for stable complex assembly involving at the interferon-β enhancer

A

Cooperative interactions

198
Q

binding of proteins at the interferon-β enhancer are aided by an architectural DNA-binding protein – () -» induces DNA bending, which helps other factors bind

A

HMG-I(Y)

199
Q

Once the enhanceosome is complete, the interferon-β gene is activated -> requirement of using a large number of proteins to activate a single gene ensures that the gene is activated only under ().

A

a very precise set of conditions

200
Q

extracellular signals trigger biochemical events whose end result is a change in gene expression

A

signaling cascades

201
Q

() respond specifically to effectors (e.g. sex hormones) that diffuse through the membrane

A

nuclear receptor proteins

202
Q

nuclear receptor proteins have (1) and (2)

A
  1. DNA-binding domain
  2. ligand-binding domain
203
Q

The first step in response to extracellular signals is often (), which triggers downstream events that lead to transcriptional changes.

A

phosphorylation

204
Q

An example of a multi-step cascade involves (), which is important in mammalian inflammatory and immune responses.

A

NF-κB

205
Q

NF-κB is a heterodimer of () proteins

A

p50 and p65

206
Q

in unstimulated cells, NF-κB is held in the cytoplasm by () -> binds to nuclear localization signal of NF-κB

A

I-κB

207
Q

in the NF-κB signaling cascade, infection triggers activation of ()

A

I-κB kinase (IKK) -> I-κB is phosphorylated

208
Q

during infection, phosphorylated I-κB is ubiquitinated by (1), and is thus targeted for degradation by the (2)

A
  1. E3 ubiquitin ligase
  2. proteasome
209
Q

degradation of I-κB exposes () of NF-κB -> allows it to move into nucleus and activate transcription

A

nuclear localization signal (NLS)

210
Q

() is where large chromosomal regions (multiple genes) are suppressed for long periods of time

A

transcriptional silencing

211
Q

allows transcriptional silencing to persist for many cell divisions

A

epigenetic inheritance

212
Q

transcriptional silencing is due to changes in ()

A

chromatin structure

213
Q

chromatin structure: (1) is often transcriptionally active, while (2) is generally silent

A
  1. euchromatin
  2. heterochromatin
214
Q

yeast chromosome III has extra copies of a and alpha genes that are not expressed:
1. a silenced copy of a is found to the right of MAT locus: (a)
2. a silenced copy of alpha is found to the left of MAT locus: (b)

A
  1. HMRa
  2. HMLalpha
215
Q

silencing of HMRa and HMRalpha depends on () -> establish and maintain heterochromatin at HML and HMR

A

silencing information regulator (Sir) proteins

216
Q

in silencing of HML and HMR, the ff proteins bind to these regions and recruit other Sir proteins

A

Abf1, Rap1, Orc1

217
Q

after extra Sir proteins are recruited to HMR and HML, they spread along the chromatin and silence the genes via the ability of (1) to (2)

A
  1. Sir2
  2. deacetylate histones
218
Q

() plays a role in establishing silencing, although its precise function is not well understood.

A

Sir1

219
Q

Sir2 is also involved in repressing RNA pol II in the regions between the () -> helps establish heterochromatic state that prevents recombination between multiple copies of these genes

A

rDNA genes

220
Q

() can mediate transcriptional silencing, as in IGF2 and H19

A

DNA modifications

221
Q

IGF2 and H19 are () -> only 1 of the parental copies of a gene is expressed

A

imprinted genes

222
Q

imprinted gene that is expressed only on paternal chromosome -> produces a growth factor needed by a developing embryo

A

IGF2

223
Q

imprinted gene that is expressed only on maternal chromosome -> makes a non-coding RNA that may play a role in cancer.

A

H19

224
Q

both IGF2 and H19 are found on ()

A

chromosome 11

225
Q

regulation of IGF2 and H19 expression is due to methylation at the ()

A

insulator control region (ICR)

226
Q

protein () can only bind to ICR when ICR is not methylated

A

CTCF

227
Q

in the maternal chromosome, ICR is (methylated/not methylated) -> CTCF is bound to ICR and blocks enhancer to prevent transcription of ICF2 but allows transcription of H19

A

not methylated

228
Q

in paternal chromosome, ICR is (methylated/not methylated) -> CTCF is not bound to ICR and thus H19 promoter is methylated and inhibits its transcription

A

methylated

229
Q

Transcription is thought to be mediated by () of the DNA, and determined by access or blocking of enhancer-bound proteins.

A

looping

230
Q

Failure of correct imprinting can lead to () – children are larger than normal at birth and are prone to cancer

A

Beckwith-Wiedemann syndrome

231
Q

Methylated DNA can recruit specific proteins. Methyl-binding domains bind specifically to ()

A

methyl-cytosine

232
Q

binds to methylated DNA and recruits Sin3A

A

MeCP2

233
Q

transcriptional co-repressor that contains a histone deacetylase

A

Sin3A

234
Q

MeCP2 represses a number of human genes – mutations in this protein can cause ()

A

Rett Syndrome

235
Q

Rett syndrome is more common in (1) because MeCP2 is found on the (2) chromosome

A
  1. girls
  2. X chromosome
236
Q

defective X chromosome responsible for Rett chromosome can also appear in males, but ()

A

since there is no extra X chromosome to mask the mutation, male fetuses don’t survive to term