The Role of the Histone Variant H2A.Z in Metazoan Development

Abstract

During the emergence and radiation of complex multicellular eukaryotes from unicellular ancestors, transcriptional systems evolved by becoming more complex to provide the basis for this morphological diversity. The way eukaryotic genomes are packaged into a highly complex structure, known as chromatin, underpins this evolution of transcriptional regulation. Chromatin structure is controlled by a variety of different epigenetic mechanisms, including the major mechanism for altering the biochemical makeup of the nucleosome by replacing core histones with their variant forms. The histone H2A variant H2A.Z is particularly important in early metazoan development because, without it, embryos cease to develop and die. However, H2A.Z is also required for many differentiation steps beyond the stage that H2A.Z-knockout embryos die. H2A.Z can facilitate the activation and repression of genes that are important for pluripotency and differentiation, and acts through a variety of different molecular mechanisms that depend upon its modification status, its interaction with histone and nonhistone partners, and where it is deposited within the genome. In this review, we discuss the current knowledge about the different mechanisms by which H2A.Z regulates chromatin function at various developmental stages and the chromatin remodeling complexes that determine when and where H2A.Z is deposited.

Incorporation of the histone variant H2A.Z counteracts gene silencing mediated by H3K27 trimethylation in Fusarium fujikuroi

“…In plants and higher eukaryotes, a correlation between histone marks, the histone variant H2A.Z, and gene transcription is evident [ 23 , 33 ]. In detail, H2A.Z colocalization with histone marks at H3 and their impact on the transcriptional output are already well described for histone H3 lysine 4 trimethylation (H3K4me3) as well as histone H3 lysine 27 trimethylation (H3K27me3) in organisms such as the model plant A. thaliana [ 36 ], mESCs [ 34 ] or the ascomycete fungus N. crassa [ 32 ].…”

“…Yet, the role of H2A.Z is still highly controversial and poorly understood. In most tested higher organisms H2A.Z is essential, except in S. cerevisiae , Schizosaccharomyces pombe , and Neurospora crassa [ 23 – 25 ] already implying fundamentally pivotal roles for the histone variant H2A.Z. In general, the incorporation of H2A.Z in the nucleosome structure is associated with manifold gene regulatory functions such as gene expression, DNA repair, chromosome stability, epigenetic memory, or cell cycle progression [ 23 , 26 – 28 ].…”

“…Next to this, crosstalk between H2A.Z and some histone marks has been implied. Here, especially a crosstalk between H2A.Z and the two opposing histone marks histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3) involved in active gene transcription and the formation of facultative heterochromatin, respectively, has been shown in metazoan systems and plants alike [ 23 , 33 ]. Briefly, in Arabidopsis , Oryza sativa , and mouse embryonic stem cells (mECs), 51%, 77%, and 92%, respectively, of all nucleosomes at promoter regions harboring H2A.Z are also decorated with H3K4me3.…”

CFDP1 regulates the stability of pericentric heterochromatin thereby affecting RAN GTPase activity and mitotic spindle formation

“…Early developmental studies using mutant mice have demonstrated that the variant histone H2A.Z is necessary for proper chromosome segregation and for the retention of the major heterochromatin protein HP1α at the PCH [ 23 – 25 ]. H2A.Z is present at both centric and PCH and contributes to centromere identity by maintaining optimal CENP-A levels at the centromere of mitotic chromosomes [ 25 , 26 ]. At centric heterochromatin, H2A.Z nucleosomes paired with dimethylated H3K4 are interspersed between CENP-A subdomains, while at the PCH, H2A.Z nucleosomes are paired with trimethylated H3K4 histones [ 27 ].…”

Anp32e protects against accumulation of H2A.Z at Sox motif containing promoters during zebrafish gastrulation

“…The histone variant H2A.Z is highly conserved across organisms and is essential for early embryogenesis in numerous animals 5,6 . H2A.Z histones are deposited primarily at gene regulatory regions within the genome, including at promoters surrounding the transcription start site (TSS) and enhancers 7,8 .…”