Epigenetics II

Question 1

Histone Methylation

Answer 1

Methylate Arg/Lys via SET domain = active mark
- H3K4me3 (KMT)
- H3K4me2 — enhance TF bind site
- H3K36me3

Question 2

Histone Demethylation

Answer 2

Demethylate Arg/Lys = repressive mark
- H3K27me3 (KDM) – promoted by PRC2
- H3K4me1 — silence in myoblast/macrophages
- H3K9me2/3 — define lamin associated domains

Question 3

Why this level of control?

Answer 3

• specific type of gene expression = fixed
• prevent improper inactivation
• genes in ready state

Question 4

Examples of Readers

Answer 4

Bromodomain – bind acetylated lysines
Chromodomian – bind methylated lysines
SANT domain – bind unmodified histones (prevent mod)

Question 5

CpG Islands

Answer 5

• associated with promoter
• where DNA methylation (cysteine residues) occurs
• hyper-methylation = no activation
• hypo-methylation = activation

Question 6

Classes of DNA Methylation Promoting Enzymes

Answer 6

DNA methyltransferase 1
- copy DNA methylation pattern during DNA synthesis
- 5Aza inhibits DMNT1

DNA methyltransferase 3A and 3B
- methylate native DNA

Question 7

2 Types of DNA Demethylation

Answer 7

Passive – inhibit DMNT + cell division
Active
- Tet1 convert methyl-CpG to hydroxy-methyl-CpG
- Base excision or Nucleotide excision repair

Question 8

Roles of DNA Methylation

Answer 8

• recruit HDAC to deacteylate histones
• block histone modifying enzymes/TFs
• inactivate X-chromosome in females
  (CpG methylate = no active Xist promoter = active X)
  (no methylate = active Xist promoter = inactive X)

Question 9

Euchromatin —> Heterochromatin

Answer 9

1) Remove H3K4me3 (active). Add H3k27me3 (repress)
2) Histone deacetylation + DNA methylation
3) Add H3K9me3 (repress)

Question 10

States in Euchromatin to Heterochromatin

Answer 10

Poised – K4 + K27 either direction

Active – K4 methylation/acetylation + hypomethylated DNA
Transition – SANT domain bind pioneer factors
Silent – K27+K9 methylation/deacetylation + hypermethylated DNA