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Review
. 2014 Sep 15;462(3):385-95.
doi: 10.1042/BJ20140754.

Chromatin and oxygen sensing in the context of JmjC histone demethylases

Alena Shmakova  1 , Michael Batie  1 , Jimena Druker  1 , Sonia Rocha  1
Affiliations
Review

Chromatin and oxygen sensing in the context of JmjC histone demethylases

Alena Shmakova et al. Biochem J. .

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 hypoxia-induced 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.

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Figures

Figure 1
Figure 1. Histone methylation marks associate with chromatin compaction status
Active chromatin or euchromatin is associated with a more open status and is characterized by several types of histone methylation marks as depicted. On the other hand, silent chromatin or heterochromatin is associated with closed and compacted status, also characterized by a subset of histone methylation patterns as depicted. JmjC enzymes can thus, in principle, control chromatin status by removing the histone methyl groups.
Figure 2
Figure 2. Schematic representation of chromatin-remodelling complexes, highlighting the domains present in different subunits
ARID, AT-rich interactive domain; HAND-SANT-SLIDE, DNA-binding domains; HSA, domain binding nuclear actin-related proteins (ARPs) and actin; NuRF, ISWI-related chromatin remodeller.
Figure 3
Figure 3. How histone methylation controls CRC recruitment
(A) Histone methylation marks localization and chromatin remodellers associated with them. bromo, bromodomain; me, methylation site. (B) Regulation of NuRD recruitment by histone methylation marks. Set9, H3K9 methyltransferase.
Figure 4
Figure 4. JmjC family domain structure and histone targets
ARID, AT-rich interactive domain; C5HC2-ZF, C5HC2 zinc finger domain; CXXC-ZF, CXXC zinc finger domain; FBox, F-box domain; JmjC, Jumonji C domain; JmjN, Jumonji N domain; LRR, leucine-rich repeat domain; TPR, tetratricopeptide domain; Tudor, Tudor domain.
Figure 5
Figure 5. Hypoxia induces the increase of certain histone methylation marks
Diagram depicting the relationship between oxygen concentration and increased levels of histone methylation marks observed in several studies.
Figure 6
Figure 6. JmjC alterations in human disease
Diagram of the observed associations of JmjC expression in different human diseases, highlighting KDM4 as particularly susceptible to deregulation in a variety of human pathologies.
See this image and copyright information in PMC

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