Developmental roles of histone H3 variants and their chaperones

Animal development and lifetime potential exploit a balance between the stability and plasticity of cellular identity. Within the nucleus, this is controlled by an interplay involving lineage-specific transcription factors and chromatin dynamics. Histone H3 variants contribute to chromatin dynamics through the timing and sites of their incorporation, promoted by dedicated histone chaperones. Moreover, their individual modifications and binding partners provide distinct features at defined genomic loci. We highlight here the importance of the H3.3 replacement variant for the nuclear reprogramming that occurs during gametogenesis, fertilization, and germline establishment. Furthermore, we describe how the recently characterized H3.3 dynamics associated with gastrulation, myogenesis, or neurogenesis underline the role of chromatin changes in cell differentiation. Finally, we discuss the challenges of maintaining centromeric identity through propagation of the centromeric CenH3 variant in different cell types. Future challenges will be to gain a comprehensive picture of H3 variants and their chaperones during development and differentiation.