HOS1-mediated activation of FLC via chromatin remodeling under cold stress

Abstract

The Arabidopsis E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE 1 (HOS1) has been shown to act as a negative regulator of cold responses by degrading the INDUCER OF CBF EXPRESSION 1 (ICE1) transcription factor through the ubiquitin/proteasome pathway. Notably, loss-of-function hos1 mutants exhibit early flowering, and the transcript level of the floral repressor FLOWERING LOCUS C (FLC) is downregulated in the mutants. However, it is largely unknown how HOS1 regulates FLC transcription. We found that HOS1 activates FLC transcription by inhibiting the activity of histone deacetylase 6 (HDA6) under cold stress. Cold temperatures induce the binding of HOS1 to FLC chromatin in an FVE-dependent manner. Cold-activated HOS1 promotes the dissociation of HDA6 from FLC chromatin, and the cold effects disappear in both hos1 and fve mutants. It is therefore clear that HOS1 regulates FLC transcription via chromatin remodeling, providing new insights into the signaling crosstalks between cold response and flowering time control.

Temperature is a major environmental factor that affects various aspects of plant growth and developmental processes. In particular, low temperatures severely limit global plant distribution and reproduction. Plants have evolved diverse cold acclimation mechanisms to sense temperature changes and increase tolerance to freezing temperatures.^1,2

Floral transition is a distinctive developmental trait that is profoundly influenced during the process of cold acclimation. A floral repressor FLOWERING LOCUS C (FLC) plays an important role in the signaling crosstalks between cold response and flowering time control. It has been found that intermittent cold treatments delay flowering time by inducing FLC expression, and the cold effects on flowering time are diminished in FLC-deficient mutants.^3,4 However, it remain largely unknown how cold temperatures regulate FLC expression.

The E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE 1 (HOS1) has been proposed to be a cold signaling attenuator that negatively regulates cold-responsive genes, such as those encoding CBF (C-repeat-binding factor) and COR (COLD-REGULATED) transcription factors.^5-7 Under cold conditions, HOS1 functions as an E3 ubiquitin ligase to trigger the degradation of INDUCER OF CBF EXPRESSION 1 (ICE1) transcription factor, a direct upstream activator of CBF3 gene.⁷ Interestingly, cold temperatures do not influence the gene expression and protein abundance of HOS1 but promote its nuclear localization.⁶

It is notable that loss-of-function hos1 mutants exhibit early flowering and the expression of FLC gene is suppressed in the mutants.^3,4 The previous studies have been focused on the role of HOS1 in cold acclimation, and molecular mechanisms underlying the HOS1-mediated regulation of FLC expression have not been explored. We have recently demonstrated that HOS1 upregulates FLC transcription by antagonizing the actions of FVE and its interacting partner histone deacetylase 6 (HDA6) under cold stress.⁸ HOS1 physically interacts with FVE, and FVE is essential for the binding of HOS1 to FLC chromatin. HOS1 inhibits the binding of HDA6 to FLC chromatin in a FVE-dependent manner (Fig. 1). Interestingly, both FVE and HDA6 are not ubiquitinated by HOS1, suggesting that HOS1 modulates FLC transcription through mechanisms other than the ubiquitination-mediated degradation of target proteins. Our observations provide a noble role of HOS1 as a chromatin remodeling factor in regulating gene transcription in response to temperature changes.

Figure 1. Dual roles of HOS1 in flowering time control under cold conditions. Under cold stress conditions, HOS1 binds to FLC chromatin via FVE and induces the dissociation of HDA6 from FLC chromatin, resulting in the activation of FLC transcription and delayed flowering. Moreover, HOS1 is involved in the control of CO abundance via an ubiquitination-mediated degradation pathway. HOS1 promotes CO degradation to inhibit the photoperiodic activation of FT under cold stress.

It should be noted that the HOS1-FVE-HDA6 regulatory module is not the sole mechanism that underlies the early flowering phenotype of hos1 mutants. It has been reported that HOS1 influences the abundance of CONSTANS (CO), a central activator of FLOWERING LOCUS T (FT), in the photoperiodic flowering pathway (Fig. 1).^9,10 HOS1 mediates CO ubiquitination to induce its degradation in response to phytochrome B-mediated red light signals as well as cold stress,^9,10 indicating that HOS1 plays a role in both light and temperature responses.

The previous and our own data demonstrate that HOS1, which is originally defined as an E3 ubiquitin ligase, is also involved in transcriptional control via chromatin remodeling, extending the repertoire of the roles of HOS1 in gene expression regulation. Given that HOS1 functions in various developmental processes, including hypocotyl elongation, primary root elongation, seed dormancy, flowering, and freezing tolerance, it is likely that HOS1 modulates the expression of a wide array of genes in plant genome via at least two distinct mechanisms: ubiquitin-mediated degradation and chromatin remodeling. In addition, it has been shown that the hos1 mutants are insensitive to changes in ambient temperatures,^10,11 supporting the role of HOS1 in ambient temperature responses. It will be interesting to examine how changes in ambient temperature and cold stress responses are coordinated by HOS1.