Chromatin and oxygen sensing in the context of JmjC histone demethylases

Abstract

Responding appropriately to changes in oxygen availability is essential for multicellular organism survival. Molecularly, cells have evolved intricate gene expression programmes to handle this stressful condition. Although it is appreciated that gene expression is co-ordinated by changes in transcription and translation in hypoxia, much less is known about how chromatin changes allow for transcription to take place. The missing link between co-ordinating chromatin structure and the hypoxiainduced transcriptional programme could be in the form of a class of dioxygenases called JmjC (Jumonji C) enzymes, the majority of which are histone demethylases. In the present review, we will focus on the function of JmjC histone demethylases, and how these could act as oxygen sensors for chromatin in hypoxia. The current knowledge concerning the role of JmjC histone demethylases in the process of organism development and human disease will also be reviewed.

Inhibitors of Enzymes Catalyzing Modifications to Histone Lysine Residues: Structure, Function and Activity

“…These KDMs have activity at both gene activating and repressing marks H3K4, H3K9, H3K27, H3K36, H3K79 and H4K20 [57]. JmjC KDMs are dependent on cellular oxygen and hypoxic cells show global increases in lysine methylation due to their i nhibition [58].…”

KDM2 Family Members are Regulated by HIF-1 in Hypoxia

“…JmjC enzymes are protein demethylases, and a number of them possess histone demethylase activity [13]. As such, these enzymes have the potential of sensing and being controlled by oxygen levels in the cell.…”

“…As such, these enzymes have the potential of sensing and being controlled by oxygen levels in the cell. Changes in histone methylation have been described in hypoxia in a number of cellular systems [13,14]. One of the JmjC enzymes, lysine (K)-specific demethylase (KDM)4E, has been analysed in terms of its oxygen dependency, revealing a similar response to oxygen to that of PHDs [15].…”

PITX1, a specificity determinant in the HIF-1α-mediated transcriptional response to hypoxia

“…As JMJD2B and PITX1 are deregulated in breast cancer, [18][19][20] we also analyzed the effect of PITX1 depletion in breast cancer cell lines. Using the same reporter system as in Fig.…”