JmjC Domain-containing Demethylase Research Articles

SF-KDM2A binds to ribosomal RNA gene promoter, reduces H4K20me3 level, and elevates ribosomal RNA transcription in breast cancer cells.

Regulation of rRNA transcription is an important factor for control of cell proliferation. We previously found that the JmjC domain-containing demethylase KDM2A reduces H3K36me2 in the rRNA gene promoter and rRNA transcription under starvation, which results in suppression of cell proliferation. The KDM2A gene also produces another protein product, SF-KDM2A, which lacks a JmjC domain and has no demethylase activity. As yet, the function of SF-KDM2A is not clear. Recently, it was reported that KDM2A was frequently amplified and that elevated expression of KDM2A was significantly associated with short survival of breast cancer patients. SF-KDM2A was more abundant than full-length KDM2A in a subset of breast cancers. In the present study, we report that SF-KDM2A localized in nucleoli and bound to the rRNA gene promoter in breast cancer cells. Overexpression of SF-KDM2A stimulated the transcription of rRNA. While the zf-CXXC domain was required for SF-KDM2A binding to the rRNA gene promoter, SF-KDM2A with mutations in the zf-CXXC domain lost the binding to the rRNA gene promoter and did not stimulate rRNA transcription. Knockdown of SF-KDM2A reduced rRNA transcription and cell proliferation. When SF-KDM2A was overexpressed, a transcriptionally repressive mark, H4K20me3, in the rRNA gene promoter was specifically reduced in a zf-CXXC domain-dependent manner, and knockdown of SF-KDM2A increased the H4K20me3 level. Taken together, these results demonstrate that SF-KDM2A binds to the rRNA gene promoter, reduces the H4K20me3 level, and activates rRNA transcription, suggesting that the stimulation of rRNA transcription by SF-KDM2A may contribute to tumorigenesis in breast cancer.

Histone Lysine Demethylases and Their Functions in Plants

Histone methylation—transfer of methyl groups to lysines or arginines residues of histone tails—plays an important role in the regulation of gene expression in eukaryotic cells. Histone methylation levels are regulated by histone methyltransferases and histone demethylases. There are two types of histone lysine demethylases (KDMs) in eukaryotes: KDM1/LSD1-like and JmjC domain-containing demethylases. KDMs can regulate gene expression directly through histone modification or indirectly through DNA methylation and siRNA regeneration. Recent studies indicate that KDMs play important regulatory roles in plant growth and developmental processes such as flowering time control, hormone response and circadian regulation.

An RNA-Seq Transcriptome Analysis of Histone Modifiers and RNA Silencing Genes in Soybean during Floral Initiation Process

Epigenetics has been recognised to play vital roles in many plant developmental processes, including floral initiation through the epigenetic regulation of gene expression. The histone modifying proteins that mediate these modifications involve the SET domain-containing histone methyltransferases, JmjC domain-containing demethylase, acetylases and deacetylases. In addition, RNA interference (RNAi)-associated genes are also involved in epigenetic regulation via RNA-directed DNA methylation and post-transcriptional gene silencing. Soybean, a major crop legume, requires a short day to induce flowering. How histone modifications regulate the plant response to external cues that initiate flowering is still largely unknown. Here, we used RNA-seq to address the dynamics of transcripts that are potentially involved in the epigenetic programming and RNAi mediated gene silencing during the floral initiation of soybean. Soybean is a paleopolyploid that has been subjected to at least two rounds of whole genome duplication events. We report that the expanded genomic repertoire of histone modifiers and RNA silencing genes in soybean includes 14 histone acetyltransferases, 24 histone deacetylases, 47 histone methyltransferases, 15 protein arginine methyltransferases, 24 JmjC domain-containing demethylases and 47 RNAi-associated genes. To investigate the role of these histone modifiers and RNA silencing genes during floral initiation, we compared the transcriptional dynamics of the leaf and shoot apical meristem at different time points after a short-day treatment. Our data reveal that the extensive activation of genes that are usually involved in the epigenetic programming and RNAi gene silencing in the soybean shoot apical meristem are reprogrammed for floral development following an exposure to inductive conditions.

HP1a Targets the Drosophila KDM4A Demethylase to a Subset of Heterochromatic Genes to Regulate H3K36me3 Levels

The KDM4 subfamily of JmjC domain-containing demethylases mediates demethylation of histone H3K36me3/me2 and H3K9me3/me2. Several studies have shown that human and yeast KDM4 proteins bind to specific gene promoters and regulate gene expression. However, the genome-wide distribution of KDM4 proteins and the mechanism of genomic-targeting remain elusive. We have previously identified Drosophila KDM4A (dKDM4A) as a histone H3K36me3 demethylase that directly interacts with HP1a. Here, we performed H3K36me3 ChIP-chip analysis in wild type and dkdm4a mutant embryos to identify genes regulated by dKDM4A demethylase activity in vivo. A subset of heterochromatic genes that show increased H3K36me3 levels in dkdm4a mutant embryos overlap with HP1a target genes. More importantly, binding to HP1a is required for dKDM4A-mediated H3K36me3 demethylation at a subset of heterochromatic genes. Collectively, these results show that HP1a functions to target the H3K36 demethylase dKDM4A to heterochromatic genes in Drosophila.

A plant-specific histone H3 lysine 4 demethylase represses the floral transition in Arabidopsis

Histone demethylation regulates chromatin structure and gene expression, and is catalyzed by various histone demethylases. Trimethylation of histone H3 at lysine 4 (H3K4) is coupled to active gene expression; trimethyl H3K4 is demethylated by Jumonj C (JmjC) domain-containing demethylases in mammals. Here we report that a plant-specific JmjC domain-containing protein known as PKDM7B (At4g20400) demethylates trimethyl H3K4. PKDM7B mediates H3K4 demethylation in a key floral promoter, FLOWERING LOCUS T (FT), and an FT homolog, TWIN SISTER OF FT (TSF), and represses their expression to inhibit the floral transition in Arabidopsis. Our findings suggest that there are at least two distinct sub-families of JmjC domain-containing demethylases that demethylate the active trimethyl H3K4 mark in eukaryotic genes, and reveal a plant-specific JmjC domain enzyme capable of H3K4 demethylation.