Table 1.
Deposition, localization, and functional properties of histone variants implicated in human cancer
| Variant | Function | Chaperones and regulatory factors |
Distribution patterns | Deposition | Mutant phenotype |
|---|---|---|---|---|---|
| H2A variant | |||||
| H2A.Z (H2A.Z.1, H2A.Z.2 and H2A.Z.2.2) |
Transcriptional regulation (mostly activation) Genome stability and chromosome segregation Telomere stability (S. cerevisiae) Others |
SRCAP complex p400 complex (including Tip60) INO80 (negative regulator, S. cerevisiae) |
TSSs, enhancers, insulators Pericentric chromatin Subtelomeric regions (S. cerevisiae) |
Replication-independent |
T.thermophila, D. melanogaster, X. Laevis, M. musculus: lethal (H2A.Z.1) S. cerevisiae, S. pombe: transcriptional defects, chromosmome loss (H2A.Z.1) |
| H2A.X | DSB repair factor recruitmenta Meiotic gene silencinga (M. musculus) |
Tip60 (D.melanogaster) FACT Nucleolin |
Genome-wide DSB sitesa |
Replication-independent DSB-induced (IRIF)a |
M. musculus: chromosomal aberrations |
| mH2A (mH2A.1 and mH2A.2) |
Transcriptional regulation (mostly repression) | ATRX (negative regulator) | Upstream and downstream of TSS Telomeres SAHFs Xi |
Replication-independent |
D. rerio: brain developmental defects (mH2A.2) M. musculus: female liver steatosis (mH2A.1) |
| H3 variant | |||||
| CENP-A | Centromere structure and function Kinetochore assembly (chromosome segregation) |
HJURP Mis18 complex |
Centromeres | Replication-independent (M/G1) | M. musculus: lethal |
| H3.3 | Gene activation Telomere homeostasis Epigenetic memory (X. laevis) Spermatogenesis (D. melanogaster) |
ATRX-Daxx HIRA DEK |
Euchromatin (active genes) Promoters and regulatory sequences Telomeric repeats Pericentric heterochromatin |
Replication-independent |
D. melanogaster, T. thermophila: sterility M. musculus (hypomorphic allele): lethality or fertility defects |
All data refer to mammalian histone variants, unless otherwise specified
a
γ-H2A.X