Introduction to Epigenetics

Question 1

DEFINE WHAT IS MEANT BY “EPIGENETIC CHANGES”.

Answer 1

Heritable changes in genome function that occur without alterations of DNA sequence

Question 2

NAME THE THREE TYPES OF EPIGENETIC CHANGES.

Answer 2

• DNA methylation
• Histone modifications
• miRNA

Question 3

EXPLAIN THE ROLE OF CPG ISLANDS IN EPIGENETIC MODIFICATION BY DNA METHYLATION.

Answer 3

• CpG islands when methylated, silence expression of the gene
• Located in the promoter region
• CpG = repeats of cysteine and guanine
• Methylation patterns are inherited during cell division

Question 4

DISCUSS THE PHENOMENON KNOWN AS “GENOMIC IMPRINTING”.

Answer 4

• Inherent only 1 working copy of a gene, the other is silenced
• Epigenetic tags are permanent except in gametogenesis

Question 5

LIST THREE DISEASES IN WHICH EPIGENETIC CHANGES PLAY A ROLE IN CARCINOGENESIS.

Answer 5

• Prader-Willi syndrome

o Deletion in paternal chromosome and the maternal copy silenced

• Angleman syndrome

o Deletion in maternal chromosome and the paternal copy is silenced

• Fragile X syndrome

o Hypermethylation of CpG island results in loss of function

Question 6

EXPLAIN THE MECHANISM BY WHICH CPG HYPERMETHYLATION CAN INCREASE CANCER RISK.

Answer 6

• Global Hypomethylation (erroneous expression)
• Hypermethylation of CpG islands for tumor suppressor genes
• Persistence of m5C residues result in spontaneous m5C to T mutations

Question 7

Key Terms:

Answer 7

Epigenetics

Epigenome

DNA methylation

Histone modifications

CpG islands

Genomic imprinting

Prader-Willi syndrome

Angleman syndrome

Fragile X syndrome

Global hypomethylation (in cancer)

DNA repair

Question 8

Important Points, Concepts and Specific Examples:

Answer 8

Epigenetic regulation is via DNA methylation, histone modifications and small inhibitory RNAs

(pp. 181, 306).

DNA methylation is the mechanism of parental/genomic imprinting; abnormalities associated with

this may result in disease states. (eg. Prader-Willi and Angelman syndromes – pp.171-173)

Fragile X syndrome is a trinucleotide repeat disorder in which the expansion of the repeats makes

the FMR1 gene susceptible to promoter methylation thus silencing the gene. (pp. 169-171)

DNA methylation in cancer – abnormal methylation patterns result in silencing of gene responsible

for maintaining control of normal cellular function (e.g. tumor suppressor genes or genes associated

with DNA repair). This results in loss of cellular control, increased susceptibility to DNA

mutations and unchecked proliferation, all features of cancer cells.

Epigenetic changes in disease states (i.e. MGMT methylation in glioblastomas) are potential

therapeutic targets.

A complex relationship between genetic and epigenetic pathways underlies both normal cellular

homeostasis and disease.