Certain mutations affecting central metabolism cause accumulation of the oncometabolite D-2-hydroxyglutarate which promotes progression of certain tumors. High levels of D-2-hydroxyglutarate inhibit the TET family of DNA demethylases and Jumonji family of histone demethylases and cause epigenetic changes that lead to altered gene expression. The link between inhibition of DNA demethylation and ...

background: some dynamic changes occurs during spermatogenesis such as histone removal and its replacement with transition nuclear protein and protamine. these proteins are required for packing and condensation of sperm chromatin. jhdm2a is a histone demethylase that directly binds to promoter regions of tnp1 and prm1 genes and controls their expression by removing h3k9 at their promoters.objec...

The genetic abnormalities that drive tumorigenesis are usually coupled with epigenetic alterations, such as DNA methylation and aberrant histone modifications, which may help oncogenic drivers accelerate cancer progression, metastasis, and therapy resistance. The discovery of histone demethylases has provided us new insight for understanding the epigenetic landscape of the chromatin environment...

Histone methylation plays fundamental roles in regulating chromatin-based processes. With the discovery of histone demethylases over a decade ago, it is now clear that histone methylation is dynamically regulated to shape the epigenome and regulate important nuclear processes including transcription, cell cycle control and DNA repair. In addition, recent observations suggest that these enzymes ...

Inhibition of histone demethylases has within recent years advanced into a new strategy for treating cancer and other diseases. Targeting specific histone demethylases can be challenging, as the active sites of KDM1A-B and KDM4A-D histone demethylases are highly conserved. Most inhibitors developed up-to-date target either the cofactor- or substrate-binding sites of these enzymes, resulting in ...

Histone methylation regulates chromatin structure, transcription, and epigenetic state of the cell. Histone methylation is dynamically regulated by histone methylases and demethylases such as LSD1 and JHDM1, which mediate demethylation of di- and monomethylated histones. It has been unclear whether demethylases exist that reverse lysine trimethylation. We show the JmjC domain-containing protein...

Since their discovery in 2004, histone demethylases have emerged as key regulators of chromatin. Recent studies have started to reveal the interconnections between histone demethylases and signaling pathways, suggesting that this interplay drives fundamental biological processes. Here, we summarize the different families and subfamilies of histone demethylases and the insights into the biologic...

Histone methylation is a reversible modification regulated by the antagonistic functions of residue-specific histone methyltransferases and demethylases. Although methylation of histone H3 at lysines 4 and 36 is linked to transcription, the roles of histone demethylases in transcription regulation are not understood. Here we show that overexpression of either Jhd1 or Rph1, two JmjC-domain prote...

Chromatin structure is dynamically modulated by various chromatin modifications, such as histone/DNA methylation and demethylation. We have reviewed histone methyltransferases and methyllysine binders in terms of small molecule screening and drug discovery in the first part of this review series. In this part, we will summarize recent progress in chemical probe and drug discovery of histone dem...