Wk4 SFM Regulation of Gene Expression

What is the simple model by which prokaryotes express genes?

Only when their products are needed

How do prokaryotes conserve resources?

Expressing metabolic genes only when their products are useful

What is a cluster of co-regulated genes?

The operon

What are the regulatory sites on the operon?

Promoter and operator

Role of the repressor?

Brake on transcriptions

Role of activator?

accelerator of transcription

What does the Z-gene on the Lac Operon code for?

B-galactosidase (prokaryotic lactase)

What does the Y-gene on the Lac Operon code for?

Galactoside permease- a transport protein that permits entry of lactose into the cell

What does the A-gene on the Lac Operon code for?

Galactoside acetyltransferase- detoxify thiogalactoside

What is the regulatory protein of the Lac Operon?

I-gene- repressor protein

Lactose controls the _____ on Lac Operon transcription?

The brake

Glucose controls the ____ on Lac Operon Transcription.

Accelerator

When lactose is absent, and glucose is HIGH, what occurs with transcription?

Repressor Bound, no transcription

When lactose is absent, and glucose is LOW, what occurs with transcription?

Repressor bound, no transcription

When lactose is present, and glucose is HIGH, what occurs with transcription?

Repressor released, transcription occurring low

When lactose is present, and glucose LOW, what occurs with transcription?

Repressor released, high transcription

When glucose is low, cAMP is high, what happens?

cAMP and CAP form a complex, which binds regulatory site on Lac Operon = increase transcription

What are the conditions for MAXIMAL lac operon transcription?

Lactose present and low glucose

What does it mean that Tryptophan acts as a co-repressor?

Low tryptophan= operon on

High tryptophan= operon off

If there is high tryptophan, what happens to the ribosome and transcription?

Ribosome does NOT stall and a terminator forms causing transcription to STOP

If there is LOW tryptophan, what happens to the ribosome and transcription?

The ribosome stalls, attenuation occurs, and transcriptions CONTINUES

What is a cis acting regulatory element?

Part of the DNA itself that functions only on a gene in the same DNA molecule

What is a trans acting regulatory element?

Diffusible molecule produced elsewhere that can regulate any accessible target

DNA binding domain tells the _____

Transcription factor where to bind

Regulatory domain determines _____

What the transcription factor does

In a reporter assay, what indicates that a deleted sequence was an enhancer?

A decrease in reporter activity

In a reporter assay, what indicates that a deleted sequence was a silencer?

An increase in reporter activity

What are the three independently functioning domains typical of a sequence-specific transcription factor?

DNA-binding domain, dimerization domain, and regulatory domain

Which transcription factor structural motif uses Zn2+ to stabilize the DNA-binding fold?

Zinc Finger

Which structural motif features a recognition helix that contacts the DNA major groove directly?

Helix-Turn-Helix (HTH)

What is the primary function of the zipper region in a leucine zipper transcription factor?

Dimerization

Which transcription factor motif has separate Dimerization and DNA-binding regions, often exemplified by MYC-MAX?

Basic Helix-Loop-Helix (bHLH)

The concept that gene expression depends on the specific mixture of regulatory factors present in a cell is called ____

Combinatorial control

In prostrate cancer, what happens with enzalutamide?

It is an androgen receptor antagonist that decreases AR dependent gene expression.

What is loosely packed form of DNA active in transcription

euchromatin

What effect does histone acetylation have on DNA accessibility?

Opens up chromatin increasing accessibility of DNA

Which enzyme class increase euchromatin by adding acetyl groups to histones?

Histone acetylases

Which enzyme class increases heterochromatin by removing acetyl groups from histones?

Histone deacetylases

What is the role of ATP in chromatin remodeling?

Provides energy to physically reposition/remove nucleosomes

RNA can change the information content of an mRNA without_____

Altering the DNA sequence

In the intestine, the APOG gene is mRNA edited to _____

Create a premature stop codon

Methylation of promoter _____ sites is commonly associated with stable transcriptional repression?

CpG

What clinical condition is associated with hypermethylation of the MLH1 promoter (CpG)?

Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

Hypermethylation of the MLH1 promoter causes a decrease in ____ repair, which leads to ____

Mismatch repair, microsatellite instability

How does the PML-RARa fusion protein cause Acute Promyelocytic Leukemia?

Maintains transcriptional repression of differentiation genes by recruiting corepressors and HDACs

What is the mechanism of ATRA (all-trans retinoic acid) treatment in Acute Promyelocytic Leukemia (APL)?

Targets PML-RARa to relieve repression and restore differentiation program

In the transferrin receptor, ____ increase the stability of mRNA

3’UTR IREs

When there is LOW iron, the mRNA is ______

Stabilized

When there is HIGH iron, the mRNA is ______

Destabilized

What proteins are needed with the Transferring receptor to aid in mRNA stability?

IRPs (iron regulatory proteins)

What is the progression of miRNA biogenesis from the nucleus to the cytoplasm?

Pri-miRNA→Drosha→Pre-miRNA→Dicer→Mature miRNA

What protein complex carries out the actual regulatory effect of microRNA?

RISC (RNA-Induced Silencing Complex)

What are the two primary ways miRNA reduces gene expression?

Translation inhibition and mRNA stability reduction (degradation)

What are P-bodies (processing bodies)?

Cytoplasmic granules composed of translationally repressed mRNAs and proteins related to mRNA decay

What two diseases are related to P-body deregulation?

ALS (scoliosis) and FTD (frontotemportal dementia)

What is the effect of eIF2a phosphorylation on gene expression especially during stress?

It inhibits translation initiation= decreased global protein synthesis

WHat is the function of stem-loops in the 5’-UTR?

Control translation

What is the function of stem-loops in the 3’UTR?

Control mRNA stability

Transferrin receptor: Low iron= IRP binds 5’UTR, causing _____ translation

Decreased

Transferrin receptor: High iron= IRE unoccupied, causing ____ translation

Increased

Term that describes changes in gene expression that do NOT involve alterations to teh underlying DNA sequence?

epigenetic regulation