The molecular mechanisms regulating gene expression are coordinated at the genome level where the accessibility of DNA sequences is determined by the structure of chromatin

The molecular mechanisms regulating gene expression are coordinated at the genome level where the accessibility of DNA sequences is determined by the structure of chromatin (van Dijk, Ding et al. 2010). Chromatin is a protein–DNA fibre consisting of repeating nucleosome units. Each nucleosome is an octamer, comprised of two copies of each of the four core histone proteins (H2A, H2B, H3 and H4) with about 150 base pairs of DNA wrapped around it. This repeating structure serves not just to compact the DNA into the tiny space of the nucleus; it also has been co-opted to regulate gene expression by virtue of its ability to selectively expose or hide DNA sequences from DNA-binding proteins, which directly regulate gene expression (Deal and Henikoff 2010).
The organization of chromatin has profound implications for the regulation of gene expression (Zhu, Dong et al. 2013) in diverse biological processes, including genome stability, recombination, developmental reprogramming, and response to external stimuli. Changes in histone variants, histone modifications as well as DNA methylation are often referred to as epigenetic regulation. However, such changes may or may not be truly epigenetic in nature because common epigenetics definition requires mitotic or meiotic heritability (Chinnusamy and Zhu 2009). H2A.Z is a conserved variant of histone H2A that has been implicated in different processes, such as transcriptional regulation, telomeric silencing, genome stability, cell cycle progression, DNA repair, and recombination (Sura, Kabza et al. 2017). Histone modification and ATP-dependent chromatin remodelling regulate chromatin structure to balance chromatin packaging and transcriptional access (Qin, Zhao et al. 2014). H2A.Z affects many processes in fungi and animals, including gene expression, recombination, and DNA repair (Xu, Leichty et al. 2018) H2A.Z is highly enriched at the transcription start site (TSS) of a large set of genes across cell types, consistent with a role in the regulation of transcription, Genome-wide studies in yeast have shown that H2A.Z enrichment at promoter-distal nucleosomes is required for initiation of transcription, while being inversely correlated with transcript levels (Sura, Kabza et al. 2017). Eukaryotic genomes possess several histone variants, and each of them confers different properties to the nucleosome, which in turn affects numerous biological processes, most commonly transcription. Histones can also be modified post-translationally and in turn affect transcription (Dai, Bai et al. 2017).
The incorporation of H2A.Z on to nucleosomes is mediated through the SWR1 complex in Arabidopsis that consists of proteins encoded by ACTIN-RELATED PROTEIN 6 (ARP6), SWC6 and PHOTOPERIOD-INDEPENDENT EARLY FLOWERING1 (PIE1) (Tasset, Yadav et al. 2018). Massive reprogramming of transcription-associated to cell differentiation during development involves activation and silencing of hundreds of genes (March-Diaz, Garcia-Dominguez et al. 2007). In plants, H2A.Z has been implicated in the response to high temperature, the phosphate starvation response, osmotic stress, the immune response, floral induction, female meiosis, recombination, thalianol metabolism, and the regulation of microRNA abundance (Qin, Zhao et al. 2014, Xu, Leichty et al. 2018). This process requires extensive changes in chromatin structure as it has been evidenced by the identification of chromatin-remodelling factors whose mutation impairs normal development at many different levels (March-Diaz, Garcia-Dominguez et al. 2007). Three main biochemical mechanisms have been reported to alter chromatin structure. The first involves the posttranslational covalent modification of the amino- and carboxy-terminal tails of histones. The pattern of chemical modifications of histones within a nucleosome (acetylation, methylation, phosphorylation, ubiquitination, and SUMOylation) seems to constitute a code that can be interpreted by other nuclear machinery (March-Diaz, Garcia-Dominguez et al. 2007). The second consists in the ATP-dependent reorganization of interactions between DNA and histones, which provokes the destabilization of the nucleosome structure. The third mechanism of chromatin remodelling lies in the substitution of canonical histones of the octamer by histone variants, which confers new stability and interactions to the nucleosome (Mizuguchi, Shen et al. 2004, Kamakaka and Biggins 2005, March-Diaz, Garcia-Dominguez et al. 2007).