molecular chapter9_3

How is eukaryotic transcription regulated?

Eukaryotic transcription is regulated by DNA-binding proteins that recruit co-activators or co-repressors.

What is the role of ELK1 in transcription regulation?

ELK1 recruits the Mediator complex (especially Med23), which bridges activators to RNA Pol II and promotes PIC assembly and transcription initiation.

How does mitogen signaling activate ELK1?

Mitogens activate MAP kinase, which phosphorylates ELK1, enabling it to recruit Mediator and HAT, enhancing transcription.

How is galactose metabolism regulated in yeast?

Gal4 activates transcription of galactose metabolism genes by binding UASG. Gal80 inhibits Gal4 unless galactose-activated Gal3 sequesters Gal80.

What co-activators does Gal4 recruit?

SAGA and Mediator complexes.

What does Ume6 do in response to nutrient conditions?

In rich nutrients, Ume6 recruits Sin3, Rpd3 (a HDAC), and Isw2 to repress transcription. Under starvation, it is phosphorylated, releasing repressors and recruiting co-activator Ime1.

What is the function of Rpd3 and Isw2?

Rpd3 is a histone deacetylase promoting compact chromatin; Isw2 is a nucleosome remodeling enzyme.

What happens at the hsp70 gene in heat shock response?

Polymerase stalls after initiation. Upon heat shock, Hsf trimerizes, binds HSEs, recruits Mediator and p-TEFb kinase, which phosphorylates RNA Pol II to resume transcription.

What is the function of HIV-1 Tat protein?

Tat binds the TAR element and recruits P-TEFb (Cdk9 + cyclin T) to phosphorylate RNA Pol II CTD and allow transcription elongation.

What is the similarity between Tat and N proteins?

Both mediate anti-termination by recruiting elongation factors to RNA polymerase, overcoming premature transcription termination.

What is combinatorial control in transcription?

A gene's expression depends on combinations of multiple regulators and signals.

What determines yeast mating types?

Four regulators (a1, α1, α2, MCM1) determine expression of a, α, and a/α-specific genes. Different MAT loci define mating type.

What is the role of MCM1 in yeast?

MCM1 is present in all cell types and activates a-specific genes alone, or interacts with α1 (to activate) and α2 (to repress).

How are a-specific genes regulated in α cells?

Repressed by MCM1 + α2.

How are α-specific genes regulated in α cells?

Activated by MCM1 + α1.

Why can a/α cells undergo meiosis but not mating?

They lack RME1 repressor, allowing meiosis, but the combination a1 + α2 represses haploid-specific and mating genes.

What is the enhanceosome in interferon-β regulation?

A stable complex of transcription factors on the enhancer, formed with help of HMG-I(Y) bending DNA, enabling precise gene control.

What are nuclear receptors and how do they work?

Proteins with DNA-binding and ligand-binding domains. Binding to steroid hormones causes conformational change, allowing recruitment of co-activators (e.g., CBP, PCAF) or co-repressors (e.g., N-CoR, SMRT).

What drug utilizes nuclear receptor pathways for therapy?

Tamoxifen, which competes with estrogen for ER binding to prevent breast cancer proliferation.

How does the NF-κB pathway activate transcription?

In unstimulated cells, NF-κB is held by I-κB. Upon infection, IKK phosphorylates I-κB, targeting it for degradation, freeing NF-κB to enter the nucleus and activate transcription.

What steps are involved in NF-κB activation?

Phosphorylation, proteolysis (ubiquitination and degradation of I-κB), and nuclear translocation of NF-κB.

What is transcriptional silencing?

A stable, heritable repression of large chromosomal regions via chromatin structure, often associated with heterochromatin.

How is mating-type gene silencing maintained in yeast?

Sir proteins (Sir2/3/4) bind near HML and HMR, deacetylate histones (e.g., H4K16 via Sir2), spreading silent chromatin.

What proteins initiate Sir complex binding?

Abf1, Rap1, and Orc1.

What is Sir2's enzymatic activity?

NAD+-dependent histone deacetylase, targeting H4K16.

How is telomeric silencing related to mating cassette silencing?

Both rely on Sir protein complexes and silent chromatin spreading.

How do IGF2 and H19 gene expression depend on methylation?

On maternal chromosome, unmethylated ICR binds CTCF, blocking enhancer from IGF2 and activating H19. On paternal chromosome, methylated ICR prevents CTCF binding, allowing IGF2 expression and repressing H19.

What is CTCF and what does it do?

A DNA-binding protein that binds unmethylated ICR, mediates enhancer-blocking and forms DNA loops.

What disease is linked to improper imprinting of IGF2/H19?

Beckwith-Wiedemann syndrome

What is MeCP2 and how does it mediate silencing?

It binds methylated DNA and recruits Sin3A co-repressor complex with HDAC activity.

What syndrome is caused by MeCP2 mutations?

Rett Syndrome, mainly affecting girls with symptoms like autism-like behaviors.