lecture 9 - Histone Modification

Question 1

What is a nucleosome?

Answer 1

A protein-DNA complex made up of two sets of 4 histone proteins.

1.5-1.7 turns of DNA are wrapped around each nucleosome

Question 2

What are Euchromatin and Heterochromatin?

Answer 2

Euchromatin: Nucleosomes are dispersed, so enzymes can easily access DNA.

Heterochromatin: Nucleosomes are compacted, so enzyme access to DNA is blocked

Question 3

What is the histone code hypothesis?

Answer 3

Modifications to histone tails are activating or repressive.

Question 4

What are some examples of histone modifications?

Answer 4

Lysine Acetylation: Active genes

H3K9 methylation: Facultative heterochromatin

H3K27 Trimethylation: Silent genes

H3K24 Trimethylation: Active genes

Question 5

How do histone modifications impact gene expression?

Answer 5

By modulating the interaction between DNA and histones

By modulating the packing of nucleosomes

By creating binding sites for effector proteins

Question 6

How does histone methylation work?

Answer 6

Any lysine residue can accept 3x methyl groups

Any arginine can accept 2x methyl groups

Only specific residues are methylated

Question 7

Name the Methyl Specific Writers

Answer 7

Protein Arginine Methyl Transferase Family
SET domain Family

Question 8

Name the Methyl Specific Erasers

Answer 8

Lysine specific demethylase
Jumonji family
Arginine deaminase

Question 9

Name the Methyl Specific Readers

Answer 9

CHROMO Domain: +ive amine causes pi-stacking interactions with aromatic groups, forming an aromatic cage.

Tudor Domain: Asp residue forms a hydrogen bond with a demethylated amine

Question 10

Describe the mechanism of SET domain methyl transferase.

Answer 10

Methyl group named SAM transferred to amine on histone lysine via a SN2 reaction

Question 11

How is product specificity maintained?

Answer 11

Monomethylasees are held in place via hydrogen bonds, so no rotation can take place, and no more methylases can be added.

In trimethylases, the Tyr is replaced by Phe, so no hydrogen bonds are formed, allowing rotation and the addition of more methyl groups.

Question 12

Give an example of allosteric regulation

Answer 12

the MLL1 SET domain contains essential residues for activity

However the lysine channel for the substrate cannot be formed in isolation

Activation of this channel requires MLL complex proteins