Genome-wide identification, classification and expression analysis of the JmjC domain-containing histone demethylase gene family in maize.

BACKGROUND: Histone methylation mainly occurs on the lysine residues and plays a crucial role during flowering and stress responses of plants, through changing the methylation status or ratio of lysine residues. Histone lysine residues of plants can arise in three forms of methylation (single, double and triple) and the corresponding demethylation can also ensue on certain occasions, by which the plants can accommodate the homeostasis of histone methylation by means of lysine methyltransferase and demethylase. The JmjC domain-containing proteins, an important family of histone lysine demethylases, play a vital role in maintaining homeostasis of histone methylation in vivo. RESULTS: In this study, we have identified 19 JmjC domain-containing histone demethylase (JHDM) proteins in maize. Based on structural characteristics and a comparison of phylogenetic relationships of JHDM gene families from Arabidopsis, rice and maize, all 19 JHDM proteins in maize were categorized into three different subfamilies. Furthermore, chromosome location and schematic structure revealed an unevenly distribution on chromosomes and structure features of ZmJMJ genes in maize, respectively. Eventually, the 19 ZmJMJ genes displayed different expression patterns at diverse developmental stages of maize based on transcriptome analysis. Further, quantitative real-time PCR analysis showed that all 19 ZmJMJ genes were responsive to heat stress treatment, suggesting their potential roles in heat stress response. CONCLUSIONS: Overall, our study will serve to present an important theoretical basis for future functional verification of JHDM genes to further unravel the mechanisms of epigenetic regulation in plants.

A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response.

The jumonji (JMJ) family of histone demethylases are Fe2+- and α-ketoglutarate-dependent oxygenases that are essential components of regulatory transcriptional chromatin complexes. These enzymes demethylate lysine residues in histones in a methylation-state and sequence-specific context. Considerable effort has been devoted to gaining a mechanistic understanding of the roles of histone lysine demethylases in eukaryotic transcription, genome integrity and epigenetic inheritance, as well as in development, physiology and disease. However, because of the absence of any selective inhibitors, the relevance of the demethylase activity of JMJ enzymes in regulating cellular responses remains poorly understood. Here we present a structure-guided small-molecule and chemoproteomics approach to elucidating the functional role of the H3K27me3-specific demethylase subfamily (KDM6 subfamily members JMJD3 and UTX). The liganded structures of human and mouse JMJD3 provide novel insight into the specificity determinants for cofactor, substrate and inhibitor recognition by the KDM6 subfamily of demethylases. We exploited these structural features to generate the first small-molecule catalytic site inhibitor that is selective for the H3K27me3-specific JMJ subfamily. We demonstrate that this inhibitor binds in a novel manner and reduces lipopolysaccharide-induced proinflammatory cytokine production by human primary macrophages, a process that depends on both JMJD3 and UTX. Our results resolve the ambiguity associated with the catalytic function of H3K27-specific JMJs in regulating disease-relevant inflammatory responses and provide encouragement for designing small-molecule inhibitors to allow selective pharmacological intervention across the JMJ family.

Comparative expression analysis of the H3K27 demethylases, JMJD3 and UTX, with the H3K27 methylase, EZH2, in Xenopus.

The regulated removal of the gene-silencing epigenetic mark, trimethylation of lysine 27 of histone H3 (H3K27me3), has been shown to be critical for tissue-specific activation of developmental genes; however, the extent of embryonic expression of its demethylases, JMJD3 and UTX, has remained unclear. In this study, we investigated the expression of jmjd3 and utx genes in Xenopus embryos in parallel with that of the H3K27 methylase gene, ezh2. At the blastula stage, jmjd3, utx and ezh2 showed similar expression patterns in the animal cap and marginal zone that give rise to the ectoderm and mesoderm, respectively. The three genes maintained similar expression patterns in the neural plate, preplacodal ectoderm and axial mesoderm during the gastrula and neurula stages. Later, expression was maintained in the developing brain and cranial sensory tissues, such as the eye and ear, of tailbud embryos. These findings suggest that the H3K27 demethylases and methylase may function continuously for progressive switching of genetic programs during neural development, a model involving the simultaneous action of both of the demethylases for the de-repression of silent genes and the methylase for the silencing of active genes.