Developmental roles of histone H3 variants and their chaperones

Abstract

Within the nucleus, chromatin dynamics with the interplay between lineage-specific transcription factors, histone dynamics, non-histone proteins and their modifications along with contribution of non coding RNA emerge as critical in defining a stable cellular identity. A fine tuning of these different parameters can impact the balance between stability and plasticity during the development and life span of a multicellular organism. At the chromatin level, dynamics of histone H3 variants through their regulated incorporation into the genome, orchestrated in time and location by dedicated histone chaperones, have gained importance in our understanding of these processes. The combination of their individual modifications and specific binding partners provide distinct features that together contribute to the establishment of genomic loci. Here, we describe the network of histone chaperones that governs their handling with a focus on deposition, to highlight how their distinct distribution impacts genome organization and function. Next, we integrate the importance of H3 variants in the context of current knowledge related to nuclear reprogramming and cell differentiation. Then, using the centromere as a paradigm, we describe a case where the identity of a given genomic locus is propagated across different cell types. Finally, to place H3 dynamics in a developmental context, we underline the role of chromatin changes in cell differentiation associated with gastrulation, myogenesis or neurogenesis.