lo 4 4. How do histone variants contribute to chromatin architecture?
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29 Terms
What are the core histones?
H2A, H2B, H3, and H4
What is the linker histone?
Histone H1
What forms the nucleosome core particle?
Two of each core histone (octamer) wrapping ~147bp of DNA
When and who was the nucleosome hypothesis proposed?
1974
Roger Kornberg
What happens when three Histone H1 coding genes are knocked out?
Global chromatin decompaction
What changes in histone modifications occur upon Histone H1 loss?
Depletion of repressive H3K27me3 and gains in active H3K36me3
What happens to A and B compartments when Histone H1 is lost?
Gains in active A compartments and reductions in repressive B compartments
How does Histone H1 facilitate spreading of repressive histone modifications?
Through compaction of nucleosomal structure at the dyad
In which cancer type are Histone H1 mutations recurrent?
B-cell lymphomas
Where do Histone H1 mutations cluster in lymphoma?
In the globular domain
What is the effect of Histone H1 mutations in lymphoma?
Dysregulation of 3D genome architecture and loss of normal histone modification deposition
Can Histone H1 mutations drive cancer formation alone?
Yes, in mouse models
How many genes encode canonical H3 proteins in humans?
15 different genes
What is H3.1?
Canonical H3 incorporated genome-wide without site-specific preferences
What is H3.3?
Canonical H3 incorporated selectively at actively transcribed regions and heterochromatin
What is CENP-A?
A non-canonical H3 variant found at centromeres
What chaperone protein incorporates CENP-A at centromeres?
HJURP
How does CENP-A differ structurally from canonical H3?
It has a shorter N-terminal alpha-helix and weaker DNA-nucleosome interactions
What happens when the CENP-A N-terminus is replaced with the canonical H3 N-terminus?
Major defects in mitosis
What are the epigenetic features of centromeres?
Low DNA methylation and low H3K9me3
What are the epigenetic features of peri-centromeric regions?
Highly enriched in DNA methylation and H3K9me3
What is macro-H2A?
A non-canonical H2A variant with a bulky C-terminal domain linked to transcriptional repression
What is H2Ax?
A non-canonical H2A variant enriched at sites of DNA damage
How many genes encode canonical H2A proteins in humans?
17 different genes encoding 10 canonical H2A proteins
What is the function of non-canonical H2A variants?
They have distinct functions in transcriptional control and DNA repair
What is the role of H3.3 in gene regulation?
It is incorporated at actively transcribed regions
What is the function of histone chaperones?
They incorporate histone variants into specific chromatin locations
What happens to CENP-A function if its N-terminal helix is extended?
Major defects in mitosis
How do histone variants contribute to chromatin architecture beyond the core histones?
They provide functional diversity and specialised roles in chromosome structure, transcriptional control, DNA repair, and mitotic function