Role of H3.3 residues in chromatin assembly and cell fate at the maternal-to-embryo transition
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE79580 | GEO | 2016/12/01
SECONDARY ACCESSION(S): PRJNA316222
REPOSITORIES: GEO
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Project description:Maternally inherited RNA and protein control much of embryonic development. The impact of such maternal information beyond embryonic development is largely unclear. Here we report that maternal contribution of histone H3.3 assembly complexes can prevent the expression of late-onset anatomical, physiologic, and behavioral abnormalities of C. elegans. We show that mutants lacking hira-1, an evolutionarily conserved H3.3-deposition factor, have severe pleiotropic defects that manifest predominantly at adulthood. These late-onset defects can be maternally rescued, and maternally derived HIRA-1 protein can be detected in hira-1(-/-) progeny. A screen for mutants that mimic the hira-1 mutant phenotype identified a HIRA complex component (PQN-80/UBN1) and a second H3.3 chaperone (XNP-1/ATRX). pqn-80 and xnp-1 abnormalities are also maternally rescued. Furthermore, mutants lacking histone H3.3 have late-onset defects similar to those of hira-1, pqn-80, and xnp-1 mutants. These data demonstrate that H3.3 assembly complexes provide non-DNA-based heritable information that can markedly influence adult phenotype. We speculate that similar maternal effects might explain the missing heritability of 2 late-onset human diseases, such as Alzheimer’s disease, Parkinson’s disease, and type 2 diabetes.
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