Insights Into the Function of the NuA4 Complex in Plants

Abstract

Chromatin remodeling plays a key role in the establishment and maintenance of gene expression patterns essential for plant development and responses to environmental factors. Post-translational modification of histones, including acetylation, is one of the most relevant chromatin remodeling mechanisms that operate in eukaryotic cells. Histone acetylation is an evolutionarily conserved chromatin signature commonly associated with transcriptional activation. Histone acetylation levels are tightly regulated through the antagonistic activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs). In plants, different families of HATs are present, including the MYST family, which comprises homologs of the catalytic subunit of the Nucleosome Acetyltransferase of H4 (NuA4) complex in yeast. This complex mediates acetylation of histones H4, H2A, and H2A.Z, and is involved in transcriptional regulation, heterochromatin silencing, cell cycle progression, and DNA repair in yeast. In Arabidopsis and, other plant species, homologs for most of the yeast NuA4 subunits are present and although the existence of this complex has not been demonstrated yet, compelling evidence supports the notion that this type of HAT complex functions from mosses to angiosperms. Recent proteomic studies show that several Arabidopsis homologs of NuA4 components, including the assembly platform proteins and the catalytic subunit, are associated in vivo with additional members of this complex suggesting that a NuA4-like HAT complex is present in plants. Furthermore, the functional characterization of some Arabidopsis NuA4 subunits has uncovered the involvement of these proteins in the regulation of different plant biological processes. Interestingly, for most of the mutant plants deficient in subunits of this complex characterized so far, conspicuous defects in flowering time are observed, suggesting a role for NuA4 in the control of this plant developmental program. Moreover, the participation of Arabidopsis NuA4 homologs in other developmental processes, such as gametophyte development, as well as in cell proliferation and stress and hormone responses, has also been reported. In this review, we summarize the current state of knowledge on plant putative NuA4 subunits and discuss the latest progress concerning the function of this chromatin modifying complex.

Keywords: Arabidopsis; NuA4; SWR1; TIP60; chromatin; development; flowering time; histone acetylation.

Figure 1

Conserved domains of the putative NuA4 subunits in plants. Proteins are grouped according to the different sub-modules of the complex: assembly platform, Piccolo NuA4, TINTIN, and SWR1 shared module. The modular architecture of the proteins was extracted from multiple alignments with the web servers HMMER v2.1 (Finn et al., 2011) and SMART (Letunic and Bork, 2018). Scale bars are indicated for the proteins of each sub-module. For the assembly platform, 200 aa; for Piccolo NuA4, TINTIN, and the SWR1 shared module, 50 aa.

Figure 2

Interaction map among NuA4 subunits in A. thaliana. The different homologs are grouped into the different sub-modules of the complex, similarly to Figure 1 . Continuous lines represent interactions demonstrated by pair-wise protein-protein experiments, whereas dotted lines depict interactions revealed in proteomic experiments.

Figure 3

Functions of the putative NuA4 subunits in different plant biological responses. Particular NuA4 subunits are involved in a number of developmental processes such as flowering transition, gametophyte development or hypocotyl growth, as well as in cell proliferation processes and stress responses or in hormone signaling transduction pathways.

Figure 4

Working models for the NuA4-dependent activation of the flowering time master regulators FLC and FT. (A) H2A.Z deposition mediated by SWR1 and histone H4 and H2A.Z acetylation performed by the putative NuA4 catalytic subunits HAM1/2 in genomic regions surrounding FLC TSS are required for FLC expression. FRI-C, together with HAM1 and a plethora of chromatin remodelers and transcriptional regulators assist in the recruitment of SWR1 to FLC chromatin, fine tuning FLC expression by facilitating the incorporation of H2A.Z and histone PTMs. (B) HAM1/2 mediate H4K5 acetylation at FT chromatin promoting its transcriptional activation. HAM1/2 interact with MRG1/2 proteins as subunits of NuA4. MRGs recognize enriched H3K36me3 regions at FT chromatin, and via their MRG domain, physically interact with CO to enhance FT activation under LD inductive photoperiods. On the other hand, SWR1 mediates the deposition of H2A.Z at the TSS of FT chromatin, modulating its expression. See text for details. Scale bars refer to the size of coding regions of the genes from their respective TSS.