13 - Cancer Epigenetics

Question 1

DNA + protein (chromatin)

Answer 1

= chromosomes

Question 2

Germ layers specified during development

Answer 2

• Ectoderm (outer layer)
• Mesoderm (middle layer)
• Endoderm (internal layer)

Question 3

Epigenetics

Answer 3

Stable & heritable, yet reversible changes in the way genes are expressed without changing their original DNA sequence

Question 4

Examples of epigenetic changes

Answer 4

• DNA methylation
• Histone modifications (acetylation/methylation)

Question 5

Waddington landscape

Answer 5

A metaphor of development, in which valleys and ridges illustrate the epigenetic landscape that guides a pluripotent cell to a well-defined differentiated state, represented by a ball rolling down the landscape.

Question 6

Epigenome remodeling during differentiation

Answer 6

• Lymphoid/myeloid development
• T helper differentiation
• Muscle stem cell differentiation
• Neural stem cell differentiation

Question 7

Four different processes can alter gene transcription through changes in chromatin

Answer 7

• Post-translational modification of histone proteins
• Variant histones
• Chromatin remodelling
• DNA methylation

Question 8

Charge of DNA

Answer 8

-

Question 9

Charge of histones

Answer 9

+

Question 10

Histone acetylation

Answer 10

• Occurs on the lysine residues of histone tails
• Neutralises the positive charge & decreases their affinity for DNA
• DNA is less tightly wound & permits transcription

Question 11

Acetylated lysine residues

Answer 11

transcriptional activation (gene expression)

Question 12

Deacetylated lysine residues

Answer 12

Transcription repression (gene silencing)

Question 13

Histone acetylase (HAT)

Answer 13

Add acetyl groups

Question 14

Histone deacetylase (HDAC)

Answer 14

Remove acetyl groups

Question 15

Histones near active genes

Answer 15

Hyperacetylated

Question 16

Epigenetic writers

Answer 16

Responsible for the addition of chemical
modifications

Question 17

Epigenetic erasers

Answer 17

Catalyse the removal of covalent modifications

Question 18

Epigenetic readers

Answer 18

Proteins with specific domains that recognize and bind to particular modifications

Question 19

Methylation

Answer 19

Methylation → condensed chromatin → transcription repressed

Question 20

Demethylation

Answer 20

Demethylation → expanded chromatin → transcription permitted

Question 21

DNA methylation and age

Answer 21

Young = more methylation
Old = more demethylation

Question 22

Leukaemia

Answer 22

Leukaemia arise from myeloid or lymphoid progenitor cells and are found in the bone marrow and blood

Question 23

Lymphoma

Answer 23

Arise from lymphatic tissue occurring mainly in lymph nodes

Question 24

Origins of cancer

Answer 24

• Environmental (smoking)
• Genetic
• Infectious disease

Question 25

How many cancer driver genes identified

Answer 25

581

Question 26

Genome-epigenome changes driving cancer

Answer 26

Many cancers show global hypomethylation and focal hypermethylation of unmethylated CpG islands

Question 27

Example of epigenetic regulatory genes that are significantly mutated in many sub-types of solid and hematological cancers

Answer 27

KMT2A-gene rearrangements

Question 28

Presence of oncogene

Answer 28

Not necessarily lead to development of cancer because a functioning tumour suppressor gene might prevent the cell from replicating.

Question 29

TSG knockout

Answer 29

If a tumour suppressor gene is knocked out but there is no oncogene present, then the cell is unlikely to be immediately cancerous

Question 30

Oncogene mutation

Answer 30

dominant gain-of-function mutations in proto - oncogenes

Question 31

How do proto-oncogenes become oncogenes

Answer 31

When expressed at increased levels, resulting from either: - Amplification leading to more copies of the gene - Translocation to a more active promotor - Mutation resulting in a fusion protein with oncogene activity

Question 32

Writing agent drugs

Answer 32

Acetylases

Question 33

Erasing agent drugs

Answer 33

Deacetylases

Question 34

Reading agent drugs

Answer 34

Bromodomain