Jumonji domain protein JMJD5 functions in both the plant and human circadian systems

Abstract

Circadian clocks are near-ubiquitous molecular oscillators that coordinate biochemical, physiological, and behavioral processes with environmental cues, such as dawn and dusk. Circadian timing mechanisms are thought to have arisen multiple times throughout the evolution of eukaryotes but share a similar overall structure consisting of interlocking transcriptional and posttranslational feedback loops. Recent work in both plants and animals has also linked modification of histones to circadian clock function. Now, using data from published microarray experiments, we have identified a histone demethylase, jumonji domain containing 5 (JMJD5), as a previously undescribed participant in both the human and Arabidopsis circadian systems. Arabidopsis JMJD5 is coregulated with evening-phased clock components and positively affects expression of clock genes expressed at dawn. We found that both Arabidopsis jmjd5 mutant seedlings and mammalian cell cultures deficient for the human ortholog of this gene have similar fastrunning circadian oscillations compared with WT. Remarkably, both the Arabidopsis and human JMJD5 orthologs retain sufficient commonality to rescue the circadian phenotype of the reciprocal system. Thus, JMJD5 plays an interchangeable role in the timing mechanisms of plants and animals despite their highly divergent evolutionary paths.C ircadian rhythms are endogenous oscillations that attune the behavior and physiology of organisms to regular changes in their environment, such as dusk and dawn. It is estimated that 1/10th of mammalian genes and one-third of Arabidopsis genes are regulated in a circadian fashion (1, 2). Not surprisingly, the circadian clock modulates a broad range of processes, ranging from the regulation of growth and flowering time in plants to the control of body temperature and the sleep-wake cycle in mammals (3, 4). The coordination of these molecular and physiological processes with the external environment has been shown to provide an adaptive advantage in organisms as diverse as cyanobacteria, higher plants, and insects (5-7).Although it is thought that circadian clocks have arisen multiple times during eukaryotic evolution (8), molecular oscillators in a diverse range of lineages share a broad overall structure consisting of interlocking transcriptional and posttranslational feedback loops (3, 4). In plants, the morning-phased Myb-like transcription factors CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY) repress the expression of TIMING OF CAB1 EXPRESSION 1 (TOC1) by binding to a conserved motif within its promoter known as the evening element (9-11). TOC1, in turn, promotes expression of CCA1 and LHY via an indirect mechanism, forming a negative feedback loop (12). This central CCA1/LHY/TOC1 loop interlocks with additional morningand evening-phased circuits to provide more robustness and flexibility to the circadian mechanism (reviewed in 3, 13).Because genes that act together are often coregulated (14), we have characterized a gene that is coexpressed with TO...

Ordered changes in histone modifications at the core of the Arabidopsis circadian clock

“…Histone demethylation has been connected with the Arabidopsis circadian clock (34,35). Although its mechanism of action remains unknown, it is plausible that H3K4me3 could serve as a substrate for histone demethylases.…”

“…A recent report has extended this analysis showing that CCA1 and LHY are also subjected to rhythmic changes in H3 acetylation and methylation (33). Histone demethylation might also be connected with the Arabidopsis circadian clock because JUMONJI DOMAIN CONTAINING 5/30 (JMD5/JMD30) loss-of-function and JMD5/JMD30-overexpressing plants affect circadian period by the clock (34,35).…”

A Constitutively Active Allele of Phytochrome B Maintains Circadian Robustness in the Absence of Light

“…Plants were then transferred to free-running conditions under red light-emitting diodes of indicated fluence rate or held in constant darkness at ZT12 of day 6 as previously described (Jones et al, 2010). Bioluminescence from groups of 10 seedlings was pooled for each data point where seedlings were transferred to constant darkness.…”

“…RNA was isolated and qRT-PCR performed as previously described (Jones et al, 2010). Samples were run in triplicate, with starting quantity estimated from critical thresholds using the standard curve of amplification.…”

Depletion of JMJD5 sensitizes tumor cells to microtubule-destabilizing agents by altering microtubule stability

“…22,23 JMJD5 was reported to function in multiple biological processes, including embryonic development, stem cell differentiation, osteoclastogenesis, circadian rhythm regulation, hepatitis B virus (HBV) replication, cell metabolism and cancer progression. [23][24][25][26][27][28][29][30][31][32] In addition, we previously reported that JMJD5 associated with the mitotic spindle and regulated mitotic spindle stability during mitosis. 33 However, it remains unclear about the functional role of JMJD5 in regulating cytoskeletal microtubule stability and its molecular mechanism.…”