Eukaryotic transcription factors

Question 1

What kind of structure do transcription factors have?

Answer 1

Modular, with distinct structural motifs

Question 2

What are 5 structural motifs common in TFs?

Answer 2

1. DNA binding
2. Dimerization
3. Interactions with RNAP or GTFs
4. Interactions with other proteins
5. Interactions with histone tails

Question 3

How are TF families grouped together?

Answer 3

Based on which conserved DNA binding motif they have

Question 4

What are 4 TF families?

Answer 4

1. Zinc finger
2. Leucine zipper
3. Basic helix-loop-helix
4. Helix-turn-helix

Question 5

What ensures sequence specificity in TFs?

Answer 5

A few specific AA near the DNA binding domain

Question 6

What are 4 mechanisms by which TFs can repress gene expression?

Answer 6

1. Competing with an activator for DNA binding space
2. Blocking the activity of an activator
3. Interacting with the general transcription machinery
4. Interact with chromatin to tighten it and block promoter access

Question 7

What are 3 mechanisms by which TFs can activate gene expression?

Answer 7

1. Directly interacting with the PIC to increase the recruitment of RNAP II or increase the recruitment of the PIC to the promoter
2. Increase the stability of the PIC’s binding to the promoter
3. Interact with the chromatin to loosen it

Question 8

What promoter elements will TFs bind to?

Answer 8

Proximal and distal elements

Question 9

Will genes be regulated by a single TF?

Answer 9

No, genes will use different combos of TFs for tight regulation of their activity

Question 10

What are enhanceosomes?

Answer 10

Large multi-protein complexes that bind to enhancers. The proteins involved are activators and DNA bending proteins

Question 11

How can enhancers provide fine-tuning of gene expression?

Answer 11

Combinatorial control. Different combos of active enhancers acting on one gene to dictate when and where it’s expressed

Question 12

What are 3 ways that TFs can be regulated themselves?

Answer 12

1. Transcriptional regulation
2. Post-translational modifications
3. Other post-translational mechanisms

Question 13

What are 3 post-transcriptional modifications that can alter the activity of TFs?

Answer 13

Protein modifications, ligand binding, protein-protein interactions and co-activators

Question 14

What are 3 other post-translational mechanisms that can alter the activity of TFs?

Answer 14

Change their activity levels by preventing or allowing them to bind to DNA, change their localization (a TF in the cytoplasm can’t do anything), alter its concentration (make more or degrade some)

Question 15

Will a TF have just one modification that turns it on and off?

Answer 15

Nope. That would be too easy. They’ll be modified in multiple ways for fine-tuned expression and activity

Question 16

What are the 4 ways that eukaryotic genes are subject to combinatorial regulation?

Answer 16

1, Different combos of TFs at proximal and distal elements

2. Different combos of chromatin structure, nucleosome positioning, and histone modifications
3. Different RNA processing
4. Regulatory RNAs