HC9 Histone variants

Question 1

histone variants

Answer 1

proteins with different amino acid composition than the standard/canonical histones. histone variants are encoded by different genes than standard histones

Question 2

canonical histones
-expressed
- adenylation?
- introns?

Answer 2

during S-phase: because DNA replication takes place, so a lot of new histones are needed.
No introns
transcripts non-polyadenylated

Question 3

non-canonical histones
-expressed
- adenylation?
- introns?

Answer 3

during the entire cell cyle. It is replication independent deposition.
contains introns
transcripts are polyadenylated

Question 4

Functions CenH3

Answer 4

is present around centromeres: is crucial for centromere functioning. It assembles the kinetochore –> which pulls sister chromatids apart into two daughter cells

CenH3 and H3 alternate at centromeres, CenH3 is present outside of centromere, H3 on inside

Question 5

functions H3.3

Answer 5

associated with transcribed genes. Enriched at
- actively transcribed genes (gets deposited at active chromatin during transcription)
- replaces lost histones.

Question 6

chaperone histones H3.3

Answer 6

HIRA deposits H3.3 at genes and regulatory sequences
DAXX deposits H3.3 at repetitive DNA/heterochromatin

Question 7

replication-coupled (RC) deposition of H3.1

Answer 7

depends on amino acids in N-terminal tail.

Question 8

Replication independent deposition of H3.3

Answer 8

only depends on 3 amino acids in histone core.

Question 9

MacroH2A
- involved in?
- location?
- looks
- role in cancer

Answer 9

• involved in X-chromosomal inactivation.
• mostly localises in inactive X-chromosomes, but also at autosomes (represses transcription of autosomes).
• Has a C-terminal domain that sticks out of nucleosomes. this is associated with HDACs and blocks chromatin remodelling.
• tumor suppressor in most cancers.

Question 10

X-chromosomal inactivation: factors involved

Answer 10

Xist RNA –> transcriptional silencing –> further silencing by H3K27me and PcG –> modifications of H3 and H4 –> macroH2A association/incorporation –> 5mC at 5’ end of genes –> irreversible inactivation.

Question 11

H2A.B
- domain
- histone modifications?
- role
- location
- co-localises with?

Answer 11

• short C-terminal domain
• does not contain common amino acids for histone modifications
• increases chromatin accessilibity
• mostly enriched in active X chromosomes. Also enriched at TSSs of actively transcribed genes.
• only 120 bp (normally 147)
• co-localises with H3: carrying activating modifications.

Question 12

H2A.X
- incorporation
- role

Answer 12

• randomly incorporated into genome
• serine residue at C-terminal extension –> DNA damage –> serine gets phosphorylated –> controls accumulation of DNA repair and chromatin remodeling proteins. The phosphorylated H2A.X needs to be removed!

Question 13

H2A.Z
- domain
- functions

Answer 13

• has an extended acidic patch domain –> affects interaction with other histones in nucleosome.
• different functions:

1. regulation of gene transcription.
   the presence of H2A.Z is needed for gene expression. During transcription it is removed, by pre-initiation complex.
2. Boundary function
   H2A.Z binds to boundary/insulator sequences. it is located between heterochromatin and euchromatin at telomeres and prevents spreading of heterochromatin.
3. Chromosome segregation
   H2A.Z is located at pericentromeric heterochromatin. it ensures genome integrity during chromosome segregation