13 - Cancer Epigenetics Flashcards

1
Q

DNA + protein (chromatin)

A

= chromosomes

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2
Q

Germ layers specified during development

A
  • Ectoderm (outer layer)
  • Mesoderm (middle layer)
  • Endoderm (internal layer)
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3
Q

Epigenetics

A

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

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4
Q

Examples of epigenetic changes

A
  • DNA methylation
  • Histone modifications (acetylation/methylation)
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5
Q

Waddington landscape

A

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.

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6
Q

Epigenome remodeling during differentiation

A
  • Lymphoid/myeloid development
  • T helper differentiation
  • Muscle stem cell differentiation
  • Neural stem cell differentiation
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7
Q

Four different processes can alter gene transcription through changes in chromatin

A
  • Post-translational modification of histone proteins
  • Variant histones
  • Chromatin remodelling
  • DNA methylation
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8
Q

Charge of DNA

A

-

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9
Q

Charge of histones

A

+

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10
Q

Histone acetylation

A
  • Occurs on the lysine residues of histone tails
  • Neutralises the positive charge & decreases their affinity for DNA
  • DNA is less tightly wound & permits transcription
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11
Q

Acetylated lysine residues

A

transcriptional activation (gene expression)

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12
Q

Deacetylated lysine residues

A

Transcription repression (gene silencing)

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13
Q

Histone acetylase (HAT)

A

Add acetyl groups

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14
Q

Histone deacetylase (HDAC)

A

Remove acetyl groups

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15
Q

Histones near active genes

A

Hyperacetylated

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16
Q

Epigenetic writers

A

Responsible for the addition of chemical
modifications

17
Q

Epigenetic erasers

A

Catalyse the removal of covalent modifications

18
Q

Epigenetic readers

A

Proteins with specific domains that recognize and bind to particular modifications

19
Q

Methylation

A

Methylation → condensed chromatin → transcription repressed

20
Q

Demethylation

A

Demethylation → expanded chromatin → transcription permitted

21
Q

DNA methylation and age

A

Young = more methylation
Old = more demethylation

22
Q

Leukaemia

A

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

23
Q

Lymphoma

A

Arise from lymphatic tissue occurring mainly in lymph nodes

24
Q

Origins of cancer

A
  • Environmental (smoking)
  • Genetic
  • Infectious disease
25
How many cancer driver genes identified
581
26
Genome-epigenome changes driving cancer
Many cancers show global hypomethylation and focal hypermethylation of unmethylated CpG islands
27
Example of epigenetic regulatory genes that are significantly mutated in many sub-types of solid and hematological cancers
KMT2A-gene rearrangements
28
Presence of oncogene
Not necessarily lead to development of cancer because a functioning tumour suppressor gene might prevent the cell from replicating.
29
TSG knockout
If a tumour suppressor gene is knocked out but there is no oncogene present, then the cell is unlikely to be immediately cancerous
30
Oncogene mutation
dominant gain-of-function mutations in proto - oncogenes
31
How do proto-oncogenes become oncogenes
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
32
Writing agent drugs
Acetylases
33
Erasing agent drugs
Deacetylases
34
Reading agent drugs
Bromodomain
35