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Gene regulation in eukaryotes I: Transcriptional and translational regulation - Regulatory transcription factors

26 important questions on Gene regulation in eukaryotes I: Transcriptional and translational regulation - Regulatory transcription factors

What are transcription factors?

Proteins that influence the ability of RNA polymerase to transcribe DNA into RNA.

Which 2 types of transcription factors play a role in the binding of the transcriptional complex to the core promoter and/or control the switch from initiation to elongation?

- General transcription factors (binding RNA polymerase to core promoter & progression to elongation);
- Regulatory transcription factors (regulate the rate of transcription of target genes).

What are 6 factors that contribute to combinatorial control?

1. Activator proteins (stimulate initiation);
2. Repressor proteins (inhibit initiation);
3. Modulation of activators and repressors by binding of small effector molecules, protein-protein interactions and covalent modifications;
4. Alteration of the composition or arrangement of nucleosomes in the vicinity of a promoter (affects transcription);
5. DNA methylation;
6. Formation of heterochromatin (C16).

What is a motif?

A domain that has a similar structure in many different proteins.

What are four examples of motifs in transcription factor proteins?

- Helix-turn-helix motif;
- Helix-loop-helix motif;
- Zinc finger motif;
- Leucine zipper motif.

How do the recognition helices in the helix-turn-helix and helix-loop-helix motifs bind to the DNA backbone?

The recognition helix often contains many positively charged amino acids, which interact with the negatively charged DNA backbone.

What do certain motifs promote?

Dimerization.

When two identical transcription factors come together, how is the formed complex called?

A homodimer.

How is it called when two different transcription factors come together?

A heterodimer.

How is the action of silencers called (inhibit transcription).

Down regulation.

How is it called when regulatory elements can function in the forward or reverse direction (2 terms)?

Orientation-independent or bidirectional.

What is surprising about the effect of regulatory elements?

They even have strong effect on the ability of RNA polymerase to initiate transcription when they are 100,000 bp away from the core promoter

Where can regulatory elements also be found?

Downstream from the promoter, sometimes in an intron.

Which two proteins control the function of mediator?

- Activators: stimulation;
- Repressors: inhibition.

How is mediator able to interact with the activator and repressor proteins, seen the fact that they can be very distant?

By the formation of a loop (Fig. 15.5 on p. 375).

Why do activator and repressor proteins have to be regulated themselves?

Because they have to function at the proper time, in the correct cell type, and under the appropriate environmental conditions.

What are the three ways in which regulatory transcription factors (activators & repressors) are controlled themselves?

- The binding of a small effector molecule;
- Protein-protein interactions;
- Covalent modification.

How could a small effector molecule work?

It binds to a regulatory transcription factor and promotes its binding to DNa.

How could a protein-protein interaction take place?

By the formation of a homodimer.

What is an example of a covalent modification?

Regulatory transcription factors can be phosphorylated, which controls their function.

What are glucocorticoid hormones?

Steroid hormones that influence nutrient metabolism in most body cells.

How could a glucocorticoid hormone effect the transcription of a protein (steps)?

- The glucocorticoid enters the cell and binds to a glucocorticoid receptor;
- HSP90 is released from the receptor;
- Two glucocorticoid receptors form a homodimer and travel into the cell nucleus;
- Two sequences in opposite directions (GRE) function as an enhancer to which the glucocorticoid receptor homodimer binds;
- The adjacent gene is activated and transcribed.

How many different genes have GREs located adjacent to them, and thereby 'react' to steroids?

Dozens of different genes.

What is different between the regulatory mechanism with steroids and most other signaling molecules?

Most signaling molecules do not enter the cell and bind directly to transcription factors, but bind to a receptor in the plasma membrane.

What is CREB protein?

CREB is cAMP response element-binding protein, a regulatory transcription factor that becomes activated when the cytoplasmic concentration of cAMP increases.

What is the mechanism of activation of CREB protein and thereby the activation of a target gene (steps)?

- A signaling molecule binds to plasma membrane receptors;
- G protein is activated, which activates adenylyl cyclase;
- Activated adenylyl cyclase catalyzes the synthesis of cAMP;
- cAMP activates kinase A;
- Kinase A phosphorylates CREB protein;
- CREB protein binds to CREB-binding protein (CBP);
- Binding with CBP leads to activation of RNA polymerase.

The question on the page originate from the summary of the following study material:

Genetics: Analysis & Principles II

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