Lecture 30

Question 1

Define epigentics

Answer 1

“Heritable” changes in phenotype that does NOT involve changes in the DNA sequence

Question 2

Explain the methylation of DNA

Answer 2

Addition of methyl groups to nucleotide bases; most common is methylation of cytosine to produce 5-methylcytosine in CpG islands; generally associated with gene repression and chromatin condensation

Question 3

Explain the acetylation of histones

Answer 3

Generally acetylated histones are associated with gene activity and open chromatin structure

Question 4

What is the histone code?

Answer 4

Critical concept of histone code hypothesis is that the histone modifications serve to recruit other proteins by specific recognition of the modified histone via protein domains specialized for such purposes; histone code is the modifications to histones (acetylation/methylation) that make up the histone code

Question 5

What are methyl transferases (3 classes)?

Answer 5

Class 1: use S adenosyl transferase (DNA methyl transferases)

Class 2: histone methyl transferases

Class 3: membrane associated

Question 6

What are demethylases?

Answer 6

Lysine demethylase (KDM 1-6): families based on structure, function, and target

Question 7

What are histone acetyl transferases (HATs)?

Answer 7

Acetylate conserved lysine AAs on histone proteins; lysine acetylation of histones modifies binding sites for specific protein-protein interaction domains

Question 8

What is the function of chromatin modifying enzymes? What are their names?

Answer 8

Alter gene expression; include:

Methyl transferases, demethylases, histone acetyl transferases, histone deacetylases

Question 9

Explain the methylation of histones

Answer 9

Methylated histones (usually a lysine) are associated with variable gene activity depending on which lysine is methylated

Question 10

Explain histone deacetylases (HDACs)?

Answer 10

Enzymes that remove acetly groups from lysine AAs on a histone, allowing the histones to wrap the DNA more tightly, generally resulting in inhibition of transcription

Question 11

Explain epigenetics in terms of monogenic disorders such as Rett Syndrome

Answer 11

A defect in the normal epigentic apparatus itself impedes normal development (is caused by a defect in the protein that recognizes methyl groups and genes are not adequately silenced)

Question 12

Explain epigentics in terms of cancer

Answer 12

Cancer involves many epigenetic lesions that could affect the pluripotent program

Question 13

Explain epigenetics in terms of ageing

Answer 13

Involves a loss of normal plasticity of response to internal and external environmental signals

Question 14

Define paramutation

Answer 14

Interaction between two alleles that leads to a heritable change in expression of one of the alleles without changing the sequence