Histone H3.3 maintains genome integrity during XXXX development.

@entity1 @entity154 @entity851 @entity2085 @entity66 @entity5 @entity19 @entity876
Histone H3.3 is a highly conserved histone H3 replacement variant in metazoans and has been implicated in many important biological processes, including cell differentiation and reprogramming. Germline and somatic mutations in H3.3 genomic incorporation pathway components or in H3.3 encoding genes have been associated with @entity1 @entity66 and @entity5 , respectively. However, the role of H3.3 in @entity1 development remains unclear. To address this question, we generated H3.3-null @entity19 models through classical genetic approaches. We found that H3.3 plays an essential role in @entity19 development. Complete depletion of H3.3 leads to @entity851 and early @entity2085 . At the cellular level, @entity19 loss triggers cell cycle suppression and cell death. Surprisingly, H3.3 depletion does not dramatically disrupt gene regulation in the developing embryo. Instead, H3.3 depletion causes dysfunction of heterochromatin structures at telomeres, centromeres, and pericentromeric regions of chromosomes, leading to @entity154 . The resulting karyotypical abnormalities and DNA damage lead to @entity876 pathway activation. In summary, our results reveal that an important function of H3.3 is to support chromosomal heterochromatic structures, thus maintaining genome integrity during @entity1 development.
