KDM4 histone demethylases catalyze the removal of methyl marks from histone lysine residues to epigenetically regulate chromatin structure and gene expression. KDM4 expression is tightly regulated to insure proper function in diverse biological processes, such as cellular differentiation. Mounting evidence has shown that disrupting KDM4 expression is implicated in the establishment and progress...

Recent discoveries of histone demethylases have shown that the dynamic regulation of histone methylation is important in differentiation and development. A paper in this issue of The EMBO Journal demonstrates that an H3K4me3 demethylase, KDM5B, is required for the regulation of self-renewal and pluripotency of embryonic stem (ES) cells by removing intragenic H3K4me3 and repressing cryptic trans...

Post-translational modification of histones plays essential roles in the transcriptional regulation of genes in eukaryotes. Methylation on basic residues of histones is regulated by histone methyltransferases and histone demethylases, and misregulation of these enzymes has been linked to a range of diseases such as cancer. Histone lysine demethylase 2 (KDM2) family proteins have been shown to e...

S tem cells are governed by epigenetic mechanisms that can either help maintain the necessary gene expression programs to preserve the stem cell state or ensure the establishment of new cell-specific expression programs during differentiation. One important level of epigenetic control originates from histone modifications such as methylation or acetylation. These modifications can be associated...

Dynamic regulation of histone modifications is critical during development, and aberrant activity of chromatin-modifying enzymes has been associated with diseases such as cancer. Histone demethylases have been shown to play a key role in eukaryotic gene transcription; however, little is known about how their activities are coordinated in vivo to regulate specific biological processes. In Drosop...

N-Methylation of histone lysine residues is an “epigenetic modification” that can be either transcriptionally activating or deactivating, depending on the position of the lysine, its methylation state and the presence of other modifications. The largest family of demethylases, the JmjC enzymes, employ 2-oxoglutarate (2OG) as a cosubstrate (Figure 1a). Some JmjC demethylases are targeted for can...

We summarize recent findings linking inflammatory hypoxia to chromatin modifications, in particular to repressive histone signatures. We focus on the role of Hypoxia-Induced Factor-1 in promoting the activity of specific histone demethylases thus deeply modifying chromatin configuration. The consequences of these changes are depicted in terms of gene expression and cellular phenotypes. We final...

The pharmacological inhibition of general transcriptional regulators has the potential to block growth through targeting multiple tumorigenic signalling pathways simultaneously. Here, using an innovative cell-based screen, we identify a structurally unique small molecule (named JIB-04) that specifically inhibits the activity of the Jumonji family of histone demethylases in vitro, in cancer cell...