Histone demethylases in chromatin biology and beyond

Abstract

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 could also have functions beyond their originally proposed role as histone demethylases. In this review, we focus on recent advances in our understanding of the molecular mechanisms that underpin the role of histone demethylases in a wide variety of normal cellular processes.

Histone Demethylase KDM6A Controls the Mammary Luminal Lineage through Enzyme-Independent Mechanisms

“…In vitro systems have provided evidence of the importance of KDM6 and its demethylase activity in establishing gene expression programs specifying lineage commitment (46). However, its in vivo roles, in particular, the specific contribution of the enzymatic activity, are less clear and possibly more nuanced.…”

Interplay between Metabolism and Epigenetics: A Nuclear Adaptation to Environmental Changes

“…There are two classes of evolutionary conserved family of histone demethylases, the LSD and the Jumonji C (JmjC)-domain containing proteins (reviewed in Dimitrova et al, 2015). LSD1, also known as KDM1A, was the first histone demethylase enzyme to be identified (Shi et al, 2004).…”

Chemical probes targeting epigenetic proteins: Applications beyond oncology

“…KDM6B has been shown to bind PcG target genes regulating their H3K27me3 levels and transcriptional activity 67 . The inhibitor of KDM6, GSK-J4, has accordingly shown potential in rheumatoid arthritis (RA) reducing production of the pro-inflammatory cytokine TNF-α from macrophages derived from RA patients 68 .…”