Regulation of gene expression 2

Question 1

Transcirptional activators have both

Answer 1

DNA binding domains and activation domains

Question 2

An example of the activation domain is the:

Answer 2

Glucocorticoid receptor: metabolism, development, and immune responses

Question 3

An exampled of the DNA binding domain is:

Answer 3

TF specificity protein 1- apoptosis, differentiation, DNA damage, etc.

Question 4

Eukaryotic transcriptional activators may have more than 1 activation domain. What is a flexible domain?

Answer 4

Allows interaction between neighboring factors even if their relative positions on the DNA are shifted

Question 5

What is the process by which the Glucocorticoid receptor enacts upon target tissue?

Answer 5

GCR binds cortisol in cytosol

Heat shock protein dissociates from receptor hormone complex, exposing nuclear localization signal

Receptors form dimer to be transported to nucleus

Inside of nucleus receptor binds glucocorticoid response element

–>Its transactivation domain binds mediator proteins and activates transcription

Question 6

In the steroid-thyroid hormone receptor:

Answer 6

Usually exists as heterodimer (TR + RXR)

Without TR dimer forms corepressor and inhibits transcription

In presence of TR coactivator is triggered to bind- activates transcription

*Lack of hormone or its receptor can result in a disease

Question 7

Nuclear receptor mutations can affect its:

Answer 7

ligand binding- there will be no effect in the presence of ligand

Coactivator binding- results in constituative binding of corepressor

*Mutations in VDR that disrupt DNA binding domain result in alopecia

Question 8

What are locus control regions (LCRs)?

Answer 8

Recruits chromatin remodeling factors and creates open chromatin

Question 9

LCRs associated with proteins

Answer 9

Control the expression of cluster genes

–>LCRs control the expression of Globin gene family

Question 10

Insulators are DNA sequences that, in association with proteins, can act as:

Answer 10

Enhancer blockers- when located between enhancer and promoter

Barriers- when located between silencer and promoter

Question 11

Mutations in LCRs can be associated with

Answer 11

Thalassemias

Question 12

Gene amplification can be used to:

Answer 12

increase the amount of gene product by increasing the number of genes available for transcription- these amplified genes provide multiple sites for transcription

Ex: rRNA and tRNA; also is a frequent genetic abnormality in human cancer cells and consists of multiple extra copies of a specific region of DNA

Question 13

The most common types of genes amiplified are:

Answer 13

oncogenes

drug resistance genes

Question 14

Gene amplification has been detected in patients receiving:

Answer 14

Methotrexate to treat cancer

–>malignant cells develop resistance by increasing number of genes for dihydrofolate reductase, the target for methotrexate

Question 15

Gene rearrangement can occur in three different mechansisms:

Answer 15

Recombination

ex: VDJ

Class switching

ex: antibodies

Alternative splicing

ex: exon skipping

Question 16

Alternative splicing in the calcitonin gene produces 2 different mRNAs for 2 different proteins:

Answer 16

Calcitonin in thyroid cells- reduces plasma calcium levels

–>increased level of calcitonin in is associated with thyroid nodule carcinoma

Calcitonin gene related protein(CGRP)- in neurons acts as a vasodilator and pain transmitter

–> increased levels of CGRP have been associated with migranes

Question 17

Abnormal splicing diseases are:

Answer 17

When mutations in splicing regulatory sequences result in disease

ex: Taupathies => disease of CNS that show accumulation of protein tau.

–>studies show mutations in tau gene to be associated with dementia and parkinsons

Question 18

Another example of abnormal splicing is:

Answer 18

LDL receptor => hypercholesterolemia

Question 19

Well known example of RNA editing

Answer 19

ApoB mRNA

Question 20

Gene expression can also be regulated through the control of mRNA degradation:

Answer 20

Nonsense-mediated degradation: triggered when ribosome stops before reaching an original STOP codon

mRNA turnover: most mRNA undergoes progressive shortening of poly A tail. loss of tail lead to rapid degradation. –>degradation catalyzed by cytoplasmic exosome from 3’ end.

ARE-mediated decay: occurs from mRNAs containing A+U rich elements. Limits halflife of mRNA to prevent overexpression of specific proteins.

Nonstop decay: assists in degradation of mRNA that lacks translation termination codon.

Question 21

Regulation of gene expressio can also occur via regulation of translation:

Answer 21

Regulatory proteins: stabilize mRNA and allow more cycles of translation

Rare codons: regulate rate of translation by having fewer copies of tRNA in the cell

miRNA: can target mRNA for degradation

Question 22

Another way gene expression can be regulated via translation is through its initiation:

Answer 22

Ferratin (main iron storage protein in cell) contains iron response element (IRE) near 5’ end of mRNA

Low iron => IRE-BP prevents translation

High iron => IRE-BP binds iron and dissociates from IRE = translation of ferritin mRNA

Question 23

The final way in which eukaryotes can reuglate gene expression is via the stability of mRNA

Answer 23

Transferrin receptor takes up transferrin (iron transporter in blood)

intracellular iron low => IRE-BP binds to IRE and prevents degradation of mRNA = more receptors

intracellular iron high => IRE-BP binds iron = release of mRNA =mRNA is degraded = less receptors