Histone H2A variants confer specific properties to nucleosomes and impact on chromatin accessibility

Abstract

In eukaryotes, variants of core histone H2A are selectively incorporated in distinct functional domains of chromatin and are distinguished by conserved sequences of their C-terminal tail, the L1 loop and the docking domain, suggesting that each variant confers specific properties to the nucleosome. Chromatin of flowering plants contains four types of H2A variants, which biochemical properties have not been characterized. We report that in contrast with animals, in Arabidopsis thaliana H2A variants define only four major types of homotypic nucleosomes containing exclusively H2A, H2A.Z, H2A.X or H2A.W. In vitro assays show that the L1 loop and the docking domain confer distinct stability of the nucleosome. In vivo and in vitro assays suggest that the L1 loop and the docking domain cooperate with the C-terminal tail to regulate chromatin accessibility. Based on these findings we conclude that the type of H2A variant in the nucleosome impacts on its interaction with DNA and propose that H2A variants regulate the dynamics of chromatin accessibility. In plants, the predominance of homotypic nucleosomes with specific physical properties and their specific localization to distinct domains suggest that H2A variants play a dominant role in chromatin dynamics and function.

The histone variant H2A.W and linker histone H1 co-regulate heterochromatin accessibility and DNA methylation

“…H2A.W promotes higher order chromatin compaction 24 and increases nucleosome stability 30 . Hence, we expected loss of H2A.W to increase heterochromatin accessibility.…”

“…Although replicative H2A nucleosomes show higher thermal stability than H2A.W nucleosomes, in vitro DNA protection assays have shown that replicative H2A confers less protection than H2A.W 30 . This indicated to us that the increase in replicative H2A at pericentromeric chromatin may not be responsible for the observed decrease in accessibility.…”

EvoChromo: towards a synthesis of chromatin biology and evolution

“…(Hake and Allis, 2006;Millar, 2013). This idea receives support from studies in plants, which deposit nucleosomes containing only a single type of H2A variant in different genomic contexts, with each variant having distinct biophysical properties (Osakabe et al, 2018;Yelagandula et al, 2014). However, it remains to be shown whether this code is sufficient to define the functions or properties of the domains marked by each type of variant.…”

Potential Functions of Histone H3.3K56 Acetylation in Mammals

“…A histone octamer contains two copies of four different types of core histones H2A, H2B, H3, and H4 [3, 4]. In addition to canonical histones, several histone variants such as H2A.Z, H2A.X, and H3.3 have also been identified, which play pivotal roles in modulating chromatin dynamics and in the activities of the underlying DNA [5–8]. Among these histone variants, H3.3 is well-known for its functions in regulating gene expression, DNA replication, and DNA repair, as well as its roles in cell cycle control, cell differentiation, development, and cancer [7, 9–13].…”

“…Lysine residues on both globular domain and tails of histones can be modified by post-translational modifications (PTMs) such as acetylation, phosphorylation, ubiquitination and methylation [2, 22–26]. These histone modifications are related to the different states of chromatin and regulate distinct histone-involved processes, including DNA replication, gene transcription and DNA repair [3, 5, 7, 13]. Histone modifications also affect chromatin assembly in various ways, including the regulation of histone folding and processing, histone nuclear import, and the interaction between histones and histone chaperones [25, 27–29].…”