Updated Mechanisms of GCN5-The Monkey King of the Plant Kingdom in Plant Development and Resistance to Abiotic Stresses

Abstract

Histone modifications are the main epigenetic mechanisms that regulate gene expression, chromatin structure, and plant development, among which histone acetylation is one of the most important and studied epigenetic modifications. Histone acetylation is believed to enhance DNA access and promote transcription. GENERAL CONTROL NON-REPRESSIBLE 5 (GCN5), a well-known enzymatic protein responsible for the lysine acetylation of histone H3 and H4, is a universal and crucial histone acetyltransferase involved in gene transcription and plant development. Many studies have found that GCN5 plays important roles in the different development stages of Arabidopsis. In terms of exogenous stress conditions, GCN5 is also involved in the responses to heat stress, cold stress, and nutrient element deficiency by regulating the related gene expression to maintain the homeostasis of some key metabolites (e.g., cellulose) or ions (e.g., phosphate, iron); in addition, GCN5 is involved in the phytohormone pathways such as ethylene, auxin, and salicylic acid to play various roles during the plant lifecycle. Some of the pathways involved by GCN5 also interwind to regulate specific physiological processes or developmental stages. Here, interactions between various developmental events and stress-resistant pathways mediated by GCN5 are comprehensively addressed and the underlying mechanisms are discussed in the plant. Studies with some interacting factors such as ADA2b provided valuable information for the complicated histone acetylation mechanisms. We also suggest the future focuses for GCN5 functions and mechanisms such as functions in seed development/germination stages, exploration of novel interaction factors, identification of more protein substrates, and application of advanced biotechnology-CRISPR in crop genetic improvement, which would be helpful for the complete illumination of roles and mechanisms of GCN5.

Keywords: ADA2b; GCN5; abiotic stress; histone modification; organ development; signaling pathways; trichome.

Figure 1

The roles and mechanisms of GCN5 in plant growth and development. In Arabidopsis, GCN5 plays different roles in the whole life cycle through different pathways. First, GCN5 interacts with ADA2b as a complex to regulate SPL3/SPL9 directly through histone acetylation to involve the juvenile-to-adult vegetative phase, which is independent of the pathway of miRNA156-SPLs action. Interestingly, GCN5 also regulates pri-miR156a expression positively. Then, a module made of GCN5, TAF1, and HD1 contributes to the photomorphogenesis and vegetative development of plants through delicate histone acetylation regulation, in which GCN5 and TAF1 function synergistically, and HD1 functions oppositely with them. HY5, the key photomorphogenesis factor is responsible for the recruitment of GCN5 and TAF1 in different ways. GCN5 interacts with HY5 genetically and functions in the same way in morphogenesis regulation. While TAF1 functions synergistically with HY5. RBCS-1A, CAB2, and IAA3 play different roles as target genes of histone acetyltransferase and histone deacetylase in this pathway. For root meristem development, GCN5, together with ADA2b, can increase transcripts of PLT1 and PLT2 by histone acetylation regulation to adjust the stem cells meristem, furthermore, ADA2b also functions independently of GCN5 to affect the stem cell niche maintenance. In rice, WOX11 can interact with ADA2b to recruit the GCN5 associated histone acetyltransferase complex and together regulate downstream PIN9, CSLF6, and other genes to facilitate the crown root meristem development. In trichome development, the GCN5-ADA2b complex regulates core genes GL1, GL2, and GL3 through histone acetylation modifications to mediate trichome initiation and branching. In the stem cuticular wax formation, GCN5 regulates the ECERIFERUM3 transcription by histone acetylation to influence cuticle membrane and wax biosynthesis. Considering the flowering, GCN5 and CLAVATA 1 regulate AG-WUS through direct histone acetylation modification to involve several floral organ developments synergistically, but the relationship between GCN5 and CLAVATA 1 is still unclear. However, it is unknown whether GCN5 affects seed development or germination associated traits. The images on the circle represent the different organs and developmental stages of Arabidopsis thaliana. GCN5 is indicated in the pink oval. The black arrows indicate active regulation, and the red bars indicate inhibition. The straight line represents the direct interaction, and the dashed line represents the indirect action. The histone acetylation modifications are represented with a graphic histone binding with the acetyl group (a red circle).

Figure 2

The mechanisms of GCN5 in plant hormone biosynthesis and secondary metabolic pathways. (A) When ethylene is absent, GCN5 and CLV1 are involved in ethylene signaling through regulating some key genes transcription (e.g., ERS1, ERF1, EBF2, CTR1) by histone acetylation, which is dependent on the EIN3 factor; meanwhile, GCN5 and CLV1 also mediate IAA3 and auxin signaling synergistically, proposing the crosslink between ethylene and auxin. But GCN5 and CLV1 show antagonistic actions on the histone acetylation of H3K9/14, which results in the up-regulation of ERS1, ERF1, EBF2, CTR1 in the clv1-1 gcn5-1 double mutant. Moreover, EIN3 can directly bind the promoters of ERF1 and EBF2 to control their transcription too (black curved arrow). (B) GCN5 regulates downstream targets MYC2, DND2, and WRKY33 expression through histone acetylation, which inhibits the SA synthesis and accumulation; on the other hand, GCN5 mediates SA synthesis through an unidentified pathway independent of NahG and ICS1 to participate in SA-mediated plant immunity. (C) GCN5 can mediate the histone acetylation level of GTL1 to affect its transcription and the associated cellulose synthesis. (D) In fatty acid synthesis, GCN5 can directly regulate histone acetylation of FAD3 and others (e.g., LACS2, LPP3) to mediate their transcription expression, and involve the different steps of fatty acid synthesis and accumulation. DAG, diacyl glycerol; TAG, triglyceride. GCN5 is indicated in the pink oval. The black arrows indicate active regulation, and the red bars indicate inhibition. The straight line represents the direct action, and the dashed line represents the indirect action. The histone acetylation modifications are represented with a graphic histone binding with the acetyl group (a red circle).

Figure 3

Underlying mechanisms of GCN5 in response to abiotic stresses and miRNA generation. (A) In response to heat stress, GCN5 directly functions on two key transcriptional factors HSFA3 and UVH6 encoding genes by histone acetylation modifications to activate their transcription, in turn, activating some heat shock protein functions and mediating plant heat resistance. (B) Encountering cold stress, CBFs recruit GCN5 and ADA2b through the DNA binding domain to activate its expression, then bind the CRT elements in the key genes COR promoter and promote transcription and increase the plant resistance to low-temperature stresses. However, the detailed mechanisms of interaction among GCN5, ADA2b, and CBFs are unclear. (C) In response to salt stress, GCN5 is up-regulated to promote the expression of downstream genes of PGX3, CTL1, MYB54 through histone acetylation, in turn, to increase salt stress tolerance. (D) In iron deficiency, GCN5 regulates directly the histone acetylation of FRD3, EXO70H2, and BOR1 to promote their expression, which in turn facilitates synthesis, transport, and homeostasis maintenance of iron in the cell. (E) In response to phosphate starvation, a long non-coding RNA (lncRNA) AT4 is up-regulated and identified as a target of GCN5 through histone H3 acetylation modifications, then downstream miR399 and its target PHOSPHATE2 is repressed and promoted respectively to mediate phosphate proper distribution. (F) GCN5 is involved in the miRNA production by regulating the miRNA machinery AGO1 and DCL1 indirectly. Further, it can also regulate some miRNA genes directly by histone acetylation modifications. GCN5 is indicated in the pink oval. The black arrows indicate active regulation, and the red bars indicate inhibition. The straight line represents the direct action, and the dashed line represents the indirect action. The histone acetylation modifications are represented with a graphic histone binding with the acetyl group (a red circle).

Figure 4

The molecular mechanisms of GCN5 involved in abiotic and biotic stresses on the genomic level. On the genomic level, the SAGA complex associated with GCN5 exerts dual and opposite effects on H3K14Ac level at the 5′ and 3′ ends of target genes as well as a positive role on H3K9Ac. Generally, the positive (e.g., COR) and negative (e.g., CNGC12, AtHIR1, and WRKY57) regulated genes are correlated with abiotic and biotic stress responses, respectively.