Lecture 12 - Transcriptional Regulation 3

Question 1

Epigenetics

Answer 1

Changes in expression in a gene or set of genes, without a change in the DNA sequence

Question 2

Two processes involved in epigenetics

Answer 2

1. DNA methylation

2. Chromosomal protein (chromatin) alterations

Question 3

Explain DNA methylation

Answer 3

1. Methyl groups are covalently added to the 5’ carbon (5’ methylcytosine) in some cytosine residues
2. DNA methyltransferase catalyzes the reaction; usually in adjacent C and G residues

Question 4

CpG islands

Answer 4

DNA regions rich in c and G doublets. Especially abundant in promoters

Question 5

Long-term epigenetic memory

Answer 5

Genomic DNA remains methylated through generations.

Question 6

Short-term epigenetic memory

Answer 6

Chromatin modifications can be reversed after a few cell division cycles

Question 7

Maintenance methylase

Answer 7

Catalyzes the formation of 5-methylcytosine int he new DNA strand

Question 8

Demethylase

Answer 8

Catalyzes the removal of the methyl group form cytosine

Question 9

Effect of DNA methylation

Answer 9

1. 5-methylcytosine still base pairs with guanine during replication and transcription
2. Extra methyl groups in a promoter attract proteins that bind methylated DNA.
   2a. These proteins are generally involved in repression of gene transcription –> heavily methylated genes tend to be inactive

Question 10

Chromatin remodellin

Answer 10

Alteration of chromatin structure

Question 11

How do histone acetyltranferases (HATs) contribute to chromatin remodelling?

Answer 11

Each histone has a tail of around 20 amino acids of which some are positively charged. HATs adds acetyl groups to these +vely charged amino acids, thus changing their charge.
The change in charge reduces the affinity of the histones for DNA, opening up the compact nucleosome. Therefore activating transcription.

Question 12

How does histone deacetylase contribute to chromatin remodelling?

Answer 12

Removes acetyl groups from histones thereby repressing transcription

Question 13

Euchromatin

Answer 13

Actively transcribed genes

Question 14

Heterochromatin

Answer 14

Genes not transcribed because of reduced accessibility

Question 15

Insulators/Boundary Elements

Answer 15

Prevent enhancers of neighboring gens to affect the expression of the gene within a chromosomal doman

Question 16

Barr Body

Answer 16

• Early in development one of the X chromosomes if inactivated
• Inactivated because it is Heterochromatinized

Question 17

How does an X chromosome become inactive?

Answer 17

1. The Xist (X-inactivation specific transcript) gene is on the X chromosome. X is heavily methylated except for this one gene
2. Transcription of Xist gene makes interference RNA
3. The RNA binds to the X chromosome from which it was transcribed
4. Methylation and histone deacetylation attract chromosomal proteins that form heterochromatin, inactivating the chromosme

Question 18

Explain how the environment can change epigenetic marks and gene expression

Answer 18

• In early embryonic cells methyltranferases are highly expressed
• In adult cells, the maintenance of DNA methylation if done mainly by the maintenance methyltransferase
• Low amounts of external methyl donor groups form dietary sources can reduce the concentrations of methyl donor SAM and can readily affect de novo DNA methylation.

Question 19

Explain genomic imprinting

Answer 19

For some genes, epigenetic DNA methylation differs in male and female gametes. As a result, an individual might inherit and allele from a female parent that is transcriptionally silenced; but the same allele from the male parent would be expressed
*Gene sequences are the same, it is the epigenetic patters that are different