FOM 5.2.2

Question 1

Where is the location of promoters and what tends to bind to it?

Answer 1

It is adjacent to the gene and is bound by general transcription factors and RNA pol II

Question 2

What are the characteristics of enhancers and silencers and where can they be located?

Answer 2

Both silencers and enhancers bind to different transcriptional regulatory proteins and effect transcription. They can be near or sometimes tens of thousands of basepairs up stream. They can also be located within introns in the gene.

Question 3

What is a lineage determining factor?

Answer 3

A transcription factor that in the presence of progenitor cells, alters the gene transcriptional program such that the cell commits to a specific lineage

Question 4

What are important domains on transcription factors?

Answer 4

DNA binding domains

Transcriptional Activation Domains

Dimerization/protein interaction domains

Question 5

What is the difference between homodimerization, heterodimerization, and hetero- or homo-multimer? What can be a benefit of these?

Answer 5

Homodimerization: transcription factor binds itself to create two-protein complex

Heterodimer: transcription factor binds a different protein to create a two-protein complex

Hetero- or homo-multimer: rather than two proteins involved in the complex, it’s 3 or more proteins.

The benefit is that it can alter ranges of DNA seqs they bind

Can lead to multiple transcriptional reg mechanisms

Question 6

What are the three mechanisms that transcription factors activate transcription from a promoter?

Answer 6

1. Recruit proteins that alter chromatin structure
2. Recruit general transcription factors
3. Recruit kinase that phosphorylates RNA pol II

Question 7

What is the role of acetylation in transcription and how can silencers take advantage of this?

Answer 7

By acetylating the histones, the DNA becomes more accessible to transcription factors (TFs) and other proteins. This tends to lead to an increase in transcription. TFs bound to silencers can recruit histone deacetylase complexes (HDACs) that lead to the deacteylation of the histons and thus repress transcription.

Question 8

What is the role of the chromatin remodeling complex?

Answer 8

Multi-protein complex which contains an ATPase subunit. Subunitys have histone modification readers. This then peels off DNA nucleosomes, or moves the histone octamer making the DNA accessible, while using ATP in the process

Question 9

What is the specific kinase that TFs recruit for RNA pol II?

Answer 9

Ptef-B

Question 10

What was the process of activation of NF-kB following a cut on Dr. Tanner’s finger?

Answer 10

Because Dr. Tanner was playing in the biohazard container like all respected doctors do he received a cut on his finger. Much similar to the puncture wound he got trying to decore an avacado.

All bacteria contain pathogen associated molecular patterns (PAMPs). PAMP activation leads to a signaling cascade which leads to the phosphorylation/degradation of inhibitor of kappa B and subsequent release of NF-kB. NF-kB then goes to the nucleus and activated transcription of pro-inflammatory genes.

Question 11

What is often the end result of a signaling pathway?

Answer 11

Activation/ repression of transcriptor factor function

Question 12

What are the methods by which glucocorticoids suppress inflammation?

Answer 12

1. Transcriptional activation of genes that produce “inflammation counteracting proteins”
2. Transrepression of pro-inflammatory genes activated by NF-kB
3. GR can act as a repressor in some contexts by directly repressing transcription

Question 13

What does the term integration of signals refer to?

Answer 13

Multiple enhancers/transcription factors can regulate a given gene

Question 14

What are the main mechanisms by which transcriptional repressor proteins repress transcription?

Answer 14

1. Block the binding of general transcription factors
2. Recruit HDAC enzymes

Question 15

What can a mutation in an enhancer site lead to?

Answer 15

It can lead to a much lower binding affinity for the transcription factor that then leads to decreased/increased transcription

Question 16

Where are most human SNPs located?

Answer 16

They are located in non-coding regions of the genome, which leads to no alteration in amino acids of proteins

Question 17

What is the determination of affinity between TF and enhancer/silencer?

Answer 17

The nucleotide sequence determines the affinity for each other

Question 18

Can SNPs that alter TF binding lead to disease and how?

Answer 18

SNPs that alter TF binding sites can influence gene transcription and lead to cell dysfunction and increased disease risk.

Question 19

The region of a transcription factor protein that interacts with chromatin remodeling complexes is known as what?

Answer 19

Transcriptional activation domain

Question 20

Specificity of protein-DNA interaction between TF and its responsive element within an enhancer is determined by?

Answer 20

Nucleotide sequence and shape of DNA

Question 21

What is the end final step before NF-kB entering the nucleus?

Answer 21

Degradation of Ik-B

Question 22

What is the difference between promoter and enhancer?

Answer 22

A promoter is where transcription initiates whereas enhancers act upon promoters increasing their activity. Enhancers can be near, far or even within a gene

Question 23

What are 4 ways that transcription factors bound to enhancers increase transcription?

Answer 23

1. Recruit histone anetyl transferases
2. Recruit chromatin remodeling complexes
3. Recruit general transcription factor
4. Recruit the RNA polymerase II kinase Ptef-B

Question 24

Inhibiting histone deactelyase can lead to what?

Answer 24

Increased gene transcription

Question 25

If a promoter sequence was mutated such that general transcription factors cannot bind how would this effect the mRNA levels in the cells?

Answer 25

There would be no mRNA of this specific gene make. It is imperative that the promoter and the TFs work togeter

Question 26

What is the purpose of having multiple enhancers and silencers for a given gene?

Answer 26

It allows for transcription to be influenced by multiple signaling pathways

Question 27

What is the purpose of the formation of heterodimers?

Answer 27

Formation of heterodimers among transcription factors alters the range of DNA sequences they can bind and/or lead to multiple transcriptional reg mechanisms

Question 28

Removal of the transcriptional activation domain will have what effect on the ability to DNA?

Answer 28

TFs are modular proteins, each domain functions independently of others. Removal of the transcriptional activation domain will not affect DNA binding of the vast majority of TFs.