FOM 5.2.2 Flashcards
Where is the location of promoters and what tends to bind to it?
It is adjacent to the gene and is bound by general transcription factors and RNA pol II
What are the characteristics of enhancers and silencers and where can they be located?
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.
What is a lineage determining factor?
A transcription factor that in the presence of progenitor cells, alters the gene transcriptional program such that the cell commits to a specific lineage
What are important domains on transcription factors?
DNA binding domains
Transcriptional Activation Domains
Dimerization/protein interaction domains
What is the difference between homodimerization, heterodimerization, and hetero- or homo-multimer? What can be a benefit of these?
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
What are the three mechanisms that transcription factors activate transcription from a promoter?
- Recruit proteins that alter chromatin structure
- Recruit general transcription factors
- Recruit kinase that phosphorylates RNA pol II
What is the role of acetylation in transcription and how can silencers take advantage of this?
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.
What is the role of the chromatin remodeling complex?
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
What is the specific kinase that TFs recruit for RNA pol II?
Ptef-B
What was the process of activation of NF-kB following a cut on Dr. Tanner’s finger?
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.
What is often the end result of a signaling pathway?
Activation/ repression of transcriptor factor function
What are the methods by which glucocorticoids suppress inflammation?
- Transcriptional activation of genes that produce “inflammation counteracting proteins”
- Transrepression of pro-inflammatory genes activated by NF-kB
- GR can act as a repressor in some contexts by directly repressing transcription
What does the term integration of signals refer to?
Multiple enhancers/transcription factors can regulate a given gene
What are the main mechanisms by which transcriptional repressor proteins repress transcription?
- Block the binding of general transcription factors
- Recruit HDAC enzymes
What can a mutation in an enhancer site lead to?
It can lead to a much lower binding affinity for the transcription factor that then leads to decreased/increased transcription
Where are most human SNPs located?
They are located in non-coding regions of the genome, which leads to no alteration in amino acids of proteins
What is the determination of affinity between TF and enhancer/silencer?
The nucleotide sequence determines the affinity for each other
Can SNPs that alter TF binding lead to disease and how?
SNPs that alter TF binding sites can influence gene transcription and lead to cell dysfunction and increased disease risk.
The region of a transcription factor protein that interacts with chromatin remodeling complexes is known as what?
Transcriptional activation domain
Specificity of protein-DNA interaction between TF and its responsive element within an enhancer is determined by?
Nucleotide sequence and shape of DNA
What is the end final step before NF-kB entering the nucleus?
Degradation of Ik-B
What is the difference between promoter and enhancer?
A promoter is where transcription initiates whereas enhancers act upon promoters increasing their activity. Enhancers can be near, far or even within a gene
What are 4 ways that transcription factors bound to enhancers increase transcription?
- Recruit histone anetyl transferases
- Recruit chromatin remodeling complexes
- Recruit general transcription factor
- Recruit the RNA polymerase II kinase Ptef-B
Inhibiting histone deactelyase can lead to what?
Increased gene transcription
If a promoter sequence was mutated such that general transcription factors cannot bind how would this effect the mRNA levels in the cells?
There would be no mRNA of this specific gene make. It is imperative that the promoter and the TFs work togeter
What is the purpose of having multiple enhancers and silencers for a given gene?
It allows for transcription to be influenced by multiple signaling pathways
What is the purpose of the formation of heterodimers?
Formation of heterodimers among transcription factors alters the range of DNA sequences they can bind and/or lead to multiple transcriptional reg mechanisms
Removal of the transcriptional activation domain will have what effect on the ability to DNA?
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.
