DNA methylation - Histone variants
10 important questions on DNA methylation - Histone variants
What is a histone variant?
- encoded throughout the cell cycle, while standard are during S phase
Difference between canonical and variants?
- expressed during DNA replication
- deposited during DNA treplication
- encoded by multiple copies, in gene clusters
- Genes do not contain introns
- Transcripts non-polyadenylated
Histone variant:
- • Typically expressed throughout cell cycle
- • Typically deposited replication-independent • Encoded by individual genes
- • Genes typically contain introns
- • Transcripts usually polyadenylated
What are the function of some well-known variants?
CENP-A - centromere function and kinetochore assembly/ centromeric chromatin
H2AX - DNA repair and recombination
H2AZ - gene expression, chromosome segregation/ active/inactive chromatin
macroH2A - transcriptional repression, X-chromosoom inactivation/ inactive chromatin
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What is the function of cenH3 (CENP-A)?
- CenH3 and H3 incorporation at centromeres alternate, and chromatin forms helical turns
What is the function of H3.3?
- Displaced H3 histones are replaced by H3.3 histones
- H3.3 prevents cryptic initiation of transcription!
- Most transcription occurs in genic regions: hence most H3.3 is incorporated into genic regions
Explain the difference between deposition of H3 and H3.3 into chromatin
H3.3 is deposited in a replication- independent manner (during & outside replication.
- HIRA histone chaperone deposits H3.3 at genes and regulatory sequences
- Daxx histone chaperone deposits H3.3 at repetitive DNA (heterochromatin)
Why is H3.3 also present at heterochromatin?
H3.3 is also present at a.o. telomeric repeats & pericentric heterochromatin (low levels)
- In repeated sequences some transcription takes place & histones can also get lost
What is the role of macro-H2A and transcriptional expression?
- Macro-H2A (mH2A) is enriched at inactive X-chromosome
- C-terminal associates with histone deacetylases (HDACs)
- blocks nucleosome remodeling
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What is the function of H2A.B?
- Enriched at active X chromosome
- Results in less stable nucleosomes that are more accessible to transcription factors & RNA pol II
- Enriched at TSSs of actively transcribed genes & appears to facilitate transcription & play role in mRNA splicing
What are the function of H2A.X?
- The phosphorylated H2A.X is replaced after DNA repair by non-phosphorylated H2A.X
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