MSI4/FVE interacts with CUL4–DDB1 and a PRC2-like complex to control epigenetic regulation of flowering time in Arabidopsis

Abstract

Flowering at the right time is crucial to ensure successful plant reproduction and seed yield and is dependent on both environmental and endogenous parameters. Among the different pathways that impinge on flowering, the autonomous pathway promotes floral transition independently of day length through the repression of the central flowering repressor FLOWERING LOCUS C (FLC). FLC blocks floral transition by repressing flowering time integrators such as FLOWERING LOCUS T (FT). MSI4/FVE is a key regulator of the autonomous pathway that reduces FLC expression. Here we report that the MSI4 protein is a DDB1 and CUL4-associated factor that represses FLC expression through its association with a CLF-Polycomb Repressive Complex 2 (PRC2) in Arabidopsis. Thus, the lack of MSI4 or decreased CUL4 activity reduces H3K27 trimethylation on FLC, but also on its downstream target FT, resulting in increased expression of both genes. Moreover, CUL4 interacts with FLC chromatin in an MSI4-dependant manner, and the interaction between MSI4 and CUL4-DDB1 is necessary for the epigenetic repression of FLC. Overall our work provides evidence for a unique functional interaction between the cullin-RING ubiquitin ligase (CUL4-DDB1 MSI4 ) and a CLF-PRC2 complex in the regulation of flowering timing in Arabidopsis.I n the model plant Arabidopsis thaliana, floral transition is regulated by changes in day length and exposure of plants to long periods of low temperature by two well-defined genetic pathways, called photoperiod and vernalization, respectively (reviewed in refs. 1-3). In addition to environmentally controlled pathways, the gibberellic acid-dependent and the autonomous pathways are controlled by internal cues, ensuring flowering independently of external signals. However, input signals that might control the activities of these pathways are currently unknown. These different pathways converge to regulate several target genes at the transcriptional level, resulting in a complex network of flowering-time regulation. Among target genes, FLOWERING LOCUS C (FLC) encodes a MADS-box transcription factor, which quantitatively blocks the floral transition by repressing the expression of the floral integrator genes SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1/AGAMOUS-LIKE 20 (SOC1/AGL20) and FLOWERING LOCUS T (FT). FLC transcriptional regulation is at the convergence of the vernalization pathway that represses FLC after exposure to low temperatures and the autonomous pathway, which constitutively represses FLC (2, 3). In turn, FLC repression results in floral integrator (i.e., FT and SOC1/AGL20) activation, leading to the induction of expression of floral-primordium-identity genes such as APETALA 1 (AP1) and LEAFY (LFY) and floralorgan-identity genes such as AGAMOUS (AG) and AP3, promoting the transition from a vegetative to an inflorescence meristem (1-3).Mutants in the autonomous pathway flower very late when grown under either long-day (LD) or short-day (SD) photoperiods (4). Cloning of the autonomous pathway gene FVE (5, 6) revealed a WD40 ...

Epigenetic regulation of Kcna3 -encoding Kv1.3 potassium channel by cereblon contributes to regulation of CD4 + T-cell activation

“…We found no global changes in H3K27 modification in CRBN-deficient CD4 + T cells (Fig. 3C), suggesting that CRBN does not regulate the global pattern of histone modifications in CD4 + T cells, similar to what has been reported about the regulation of histone modification by MSI4/FVE (12).…”

“…Moreover, we noticed that Cul4A and DDB1 fail to be recruited to the Kcna3 chromatin in the absence of CRBN. This finding is significant, because Cul4A and DDB1 are components of the CRBN E3 ubiquitin ligase complex that not only participate in ubiquitin ligase activity, but also are involved in H3K27 modifications, such as H3K27me3 and H3K27ac (12,15). We found that CRBN is responsible for EZH1 (a histone methyltransferase for H3K27 modification) recruitment to Kcna3 chromatin.…”

“…Recent studies have shown that Cul4A, which binds to CRBN, plays a role in histone modification (12)(13)(14)(15). Moreover, analysis of the relative levels of Cul4A transcripts in multiple tissue types using the Novartis BioGPS expression array database (9) revealed that, like CRBN, Cul4A is expressed to the greatest extent in lymphoid cells (including CD4 + T cells) compared with other cell types (Fig.…”

An E3 ligase complex regulates SET-domain polycomb group protein activity in Arabidopsis thaliana

“…Alterations in PcG complex composition and association to chromatin may be beneficial as organisms undergo developmental transitions and respond to their environment, however (4,13). There is increasing evidence for regulation of PRC2 activity by posttranslational modifications of PcG proteins by E3 ubiquitin ligases (14,15). Here, we show that CLF SETdomain activity is regulated at the posttranslational level by UPWARD CURLY LEAF1 (UCL1), the F-box component of an E3 ligase that binds CLF and targets it for degradation via the ubiquitin-26S proteasome pathway.…”

Chloroplast retrograde signal regulates flowering

“…An earlier study demonstrated that FVE plays dual roles in flowering regulation and cold acclimation to provide evolutionary fitness to plants in sensing intermittent cold stress (41). In addition, FVE is also implicated in the photoperiod flowering pathway and is postulated to bind chromatin as a large protein complex of ∼1.0 MDa (54,55). Thus, it is likely that these versatile functions of FVE in environment-controlled flowering are achieved through specific interactions with distinct partners like HOS1 and CUL4-DDB1 (54,56).…”