L25 Regulation Of Gene Expression And Its Modification

Question 1

What is meant by regulation of gene expression

Answer 1

Control on amount of protein being expressed by genetic DNA

Question 2

What are types of gene expression

Answer 2

▪️Constitutive:unvarying expression of a gene(eg genes expressing glycolysis enzymes
▪️Regulated:expression of genes which the cellular level of their products varies in response to molecular signals (ex stress,infection)
Can be inducible or repressible

Question 3

What are inducible genes

Answer 3

Genes which their product inc in concentration under particular molecular circumstances i.e: positive regulation

Question 4

What are repressible genes

Answer 4

Genes in which their products decrease in concentration in response to molecular signals

Question 5

What are the different levels at which gene regulation can occur

Answer 5

Level of chromatin
Level of DNA
Level of transcription 
Post transcription
Level of translation
Post translation

Question 6

Explain how gene regulation can occur at level of chromatin

Answer 6

▪️Euchromatin contains histone proteins that have been covalently modified at their amino terminal ends(acetylation or phosphorylation) inc negative charge on histones and cause them to be loosely attached to DNA relaxing the nucleosome and allowing transcription factors to bind to specific regions

▪️methylation can occur on cytosine bases in promoter region and the more transcriptionally active the less methylated a gene is

Question 7

How can drugs affect Gene expression (methylation)

Answer 7

By inducing DNA methylation or histone modification as the use of histone deacetylase inhibitors to kill cancer cells

Question 8

How can gene regulation occur at level of DNA

Answer 8

1-amount of DNA
2-rearrangement of DNA
3-mobile DNA elements(transposons)

Question 9

Amount of DNA

Answer 9

Inc or dec in number of copies of a gene can affect the amount of gene product produced

Question 10

Give an example of gene amplification

Answer 10

Gene coding for enzyme dihydrofolate reductase required for synthesis of thymidine triosephosphate

Question 11

How can cancer cells develop resistance to anti cancer drugs

Answer 11

By gene amplification, the anti cancer drug methotrexate acts by inhibiting enzymes dihydrofolate reductase
Amplification of DHFR genes by cancer cells makes them less responsive to methotrexate

Question 12

Rearrangement of DNA

Answer 12

Ex: immunoglobulins
They can produce from 109-1011 diff immunoglobulins
For diversity
IG chain contains: C,V,D,J
each time and Ig is produced the rearrangement is diff but constant remains

Question 13

Mobile DNA elements

Answer 13

Move in random manner from one side to another on same or different chromosome
Movement meditated by transposase

Question 14

How can gene regulation occur at level of transcription

Answer 14

For transcription factors to work they have to interact in harmony with DNA sequences acting as regulatory regions:
1-Basal expression elements
2-regulated expression elements
3-response elements

Question 15

Basal expression elements

Answer 15

Consists of proximal element of TATA box that direct RNA polymerase 2 to correct start site and
Upstream element CAAT box that specify frequency of initiation

Question 16

Regulated expression elements

Answer 16

Specific DNA sequences that are present in same gene (cis element)
Responsible for regulation of expression

Can exert effect on transcription even if thousands of bases away from promoter (include enhancers and silencers)

Question 17

Regulatory proteins(trans factors)

Answer 17

Activators and inhibitors as they are produced by other genes than this being transcribed

Question 18

Response elements

Answer 18

Sequences on DNA which signaling molecules bind causing change in gene expression
They can bind to intracellular receptors or to cell surface receptors

Question 19

How can post transcriptional regulation occur

Answer 19

Regulation can occur during processing of primary transcript and during transport of mRNA from nucleus to cytoplasm
▪️Alternative splicing and polyadenylation sites
▪️Rna editing
▪️Stability of mRNA

Question 20

Alternative splicing and polyadenylation sites

Answer 20

Sometimes alternative splicing and polyadenylation of sites causes diff proteins to be produced from same gene
Ex: calcitonin gene in thyroid can undergo alternative solicing and polyadenylation to be produce a diff protein called CGRP

Question 21

RNA editing

Answer 21

Processing of RNA in nucleus by enzymes that change a single nucleotide either by insertion,deletion or substitution

Question 22

Give an example for RNA editing

Answer 22

Beta apoprotein(many versions)
Liver and intestinal cells

Question 23

Stability of mRNA

Answer 23

Developmental or environmental stimuli like nutrient levels,cytokines,hormones and temp shifts as well as env stresses affect mRNA stability which affects amount of protein produced

Question 24

Explain pharmacological modulation of post transcriptional events

Answer 24

Achieved by interfering with mRNA by using small complementary oligonucleotide that can block its translation (antisense oligonucleotide)
Used in some genetic disorders

Question 25

How can regulation at level of translation take place

Answer 25

Action of eIF2 can be inhibited by phosphorylation thus inhibiting translation

Question 26

How does post translation regulation work

Answer 26

Half lives

Regulated by proteolytic degradation

Question 27

Explain the mechanism of protease inhibitors

Answer 27

Saquinvir:anti viral that inhibits post translational processing of precursor viral proteins (HIV and hep C

Question 28

Explain method or action of proteasome inhibitors

Answer 28

Bortezomib, used in treatment of specific types of cancer by inhibiting specific protein degradation which accumulates to induce cancer cell death