13 | Network Motifs

Question 1

What are DORs?

Answer 1

• Dense Overlapping Regulons - high connectivity
• specific type of network motif found in gene regulatory networks.
• dense network of interactions, multiple TFs regulate overlapping sets of genes.

Question 2

Regulation of gene expression by transcription factors

K_G?

Answer 2

Rate of transcription for the gene with no TF bound.

Question 3

Regulation of gene expression by transcription factors

K_TF:G?

Answer 3

Rate of transcription for the gene when TF is bound

Question 4

Fractional occupancy approximation

Explain the concept

Answer 4

• method used to describe how occupancy of a DNA binding site by TF depends on its conc.
• It helps to predict how TF binding affects gene expression.

Question 5

Fractional occupancy approximation

f_G(TF)?

Answer 5

Fractional occupancy for unbound TF
= K_{sdubb / ( Ksdubb + TF)}

Question 6

Fractional occupancy approximation

f_TF:G(TF)?

Answer 6

Fractional occupancy for bound TF
= TF / ( K_{sdubb + TF)}

Question 7

Fractional occupancy approximation

f_G(TF) + f_TF:G(TF) = ?

Answer 7

1

Question 8

Fractional occupancy approximation
k_syn(TF) ?

Answer 8

= f_G(TF)k_G + f_TF:G(TF)k_TF:G = ?

Question 9

Fractional occupancy approximation

K_d ?

Answer 9

K_d = k_off / k_on
(for binding of TF to G)

Question 10

Further levels of regulation other than simple TF?

Answer 10

• Sigmoidal rather than hyperbolic dependency (cooperativity) (eg O2 binding to Haemoglobin)
• Transcription regulators (TR)
  
  • Transcription factor activation (eg NFkB)
  • Transcription factor deactivation
  • Competitive binding to the transcription factor

Question 11

Simple regulation - activator

Answer 11

k_TF:G vs k_G ?
k_TF:G > k_G

Question 12

Simple regulation - repressor

Answer 12

k_TF:G vs k_G ?
k_TF:G < k_G

Question 13

Positive autoregulation

Answer 13

k_G:G vs k_G ?
k_G:G > k_G

Question 13

Negative autoregulation

Answer 13

k_G:G vs k_G ?
k_G:G < k_G

Question 14

Negative autoregulation - effect?

Answer 14

NAR →
- fast response time, but the rate is decreased.
- at start X will be produced very quickly, the rate will decrease as more X is present
Alon claims:
- NAR decreases cell-to-cell variability
- However, if the negative autoregulation feedback contains a long delay then noise can also be amplified.

Question 15

Positive autoregulation - effect?

Answer 15

PAR →
- slower response time
- maximum rate is reached only after enough of X is present
Alon claims:
- positive autoregulation increases cell-to-cell variability
- strong positive autoregulation creates bimodal distributions

Question 16

The ___________ of a transcription factor-regulated gene can be described via a _________ , and the latter requires the computation of _______________.

(ungraded quiz)

Answer 16

Transcription rate, gene expression model, fractional occupancies

Question 17

Consider the NFκB model. Which role(s) does the transcriptional regulator IκBn exert in this model?
a. Binding to the bound transcription factor
b. Transcription factor activation
c. Transcription factor deactivation

(ungraded quiz)

Answer 17

a. Binding to the bound transcription factor
c. Transcription factor deactivation

Question 18

Consider the competitive binding of two transcription factors TF₁ and TF₂ (with dissociation constants K_d,1=1nM and K_d,2=2nM, respectively) to the promoter of a gene G, available as a single copy.

Assume concentrations of TF₁=1nM and TF₂=1nM, respectively, and that there are no cooperative effects.

What is the fractional occupancy f_TF1 of the promoter of gene G with TF₁?

(ungraded quiz - unlikely to be asked?)

Answer 18

f_TF1 = (TF₁ / K₁) / (1 + (TF₁ / K₁) + (TF₂ / K₂) = 0.4

Question 19

Which of the following information-processing mechanisms can be achieved with feedforward loops?

a.Lowering response times
b.Filtering of information
c.Memory

(ungraded quiz)

Answer 19

a.Lowering response times
b.Filtering of information

Question 20

Which motifs can filter out transient signals?

(ungraded quiz)

Answer 20

Coherent type 1 FFL

Question 21

Which motifs can enhance transient signals?

Answer 21

Double-negative feedback loop
Double-positive feedback loop

Question 22

Which of the following characteristics are typical for a double-negative feedback loop?
◦ Turns transient stimulus into persistent signal
◦ Creates oscillations
◦ Generates pulses
◦ Accelerates responses
◦ Has a sign-sensitive delay
◦ Behaves like a switch toggled by the input

(2023_1, 2020_2)

Answer 22

◦ Turns transient stimulus into persistent signal
◦ Behaves like a switch toggled by the input

Question 23

FFL
Incoherent vs coherent
What are the four types, considering X’s effect on Y and Z?
For (Y,Z)

(stevie mnemonic)

Answer 23

Type 1: (1,1)
Type 2: (0,0)
Type 3: (1,0)
Type 4: (0,1)

Question 24

FFL
Inchoherent vs coherent
What is Y’s interaction with Z in each of the types?
coherent types (1,2,3,4)
incoherent types (1,2,3,4)

Answer 24

(1,1,0,0)
(0,0,1,1)

Question 25

FFL

Consider the regulation of gene z by two transcription factors X and Y at independent promotor sites.

Name all possible promotor states

(2022_2)

Answer 25

(P1,P2)
(P1:X, P2)
(P1, P2:Y)
(P1:X, P2:Y)

Question 26

FFL
Consider the regulation of gene z by two transcription factors X and Y at independent promotor sites, with possible promotor states (P1,P2); (P1:X, P2), (P1, P2:Y), (P1:X, P2:Y).
Assume that in each promoter state, transcription is either fully active or inactive (no transcription).
Enumerate the active states if this is the following type of FFL:
C1-FFL (AND)

(2022_2)

Answer 26

(P1:X, P2:Y)

Question 27

FFL
Consider the regulation of gene z by two transcription factors X and Y at independent promotor sites, with possible promotor states (P1,P2); (P1:X, P2), (P1, P2:Y), (P1:X, P2:Y).
Assume that in each promoter state, transcription is either fully active or inactive (no transcription).
Enumerate the active states if this is the following type of FFL:
C1-FFL (OR)
(2022_2)

Answer 27

(P1:X, P2)
(P1, P2:Y)
(P1:X, P2:Y).

Question 28

FFL
Consider the regulation of gene z by two transcription factors X and Y at independent promotor sites, with possible promotor states (P1,P2); (P1:X, P2), (P1, P2:Y), (P1:X, P2:Y).
Assume that in each promoter state, transcription is either fully active or inactive (no transcription).
Enumerate the active states if this is the following type of FFL:
I1-FFL (AND)
X → Y, Z
Y ┴ Z

(2022_2)

Answer 28

(P1:X, P2)

Question 29

FFL
Consider the regulation of gene z by two transcription factors X and Y at independent promotor sites, with possible promotor states (P1,P2); (P1:X, P2), (P1, P2:Y), (P1:X, P2:Y).
Assume that in each promoter state, transcription is either fully active or inactive (no transcription).
Which of these motifs could also be realized with overlapping promotors, i.e. if it is impossible for transcription factors X and Y to bind simultaneously?
C1-FFL (AND)
C1-FFL (OR)
I1-FFL (AND)
(2022_2)

Answer 29

C1-FFL (OR)
I1-FFL (AND)

Question 30

Exercise 1: Quiz 5. Which of the following characteristics are typical for the incoherent type 1 feedforward loop with AND gate?
□ Turns transient stimulus into persistent signal
□ Creates oscillations
□ Generates pulses
□ Accelerates responses
□ Has a sign-sensitive delay
□ Behaves like a switch toggled by the input.
(2020_1)

Answer 30

□ Generates pulses
□ Accelerates responses

(maybe also □ Has a sign-sensitive delay according to chatgpt?)