Abstract
Epigenetic changes are well-established contributors to cancer progression and normal developmental processes. The reversible modification of histones plays a central role in regulating the nuclear processes of gene transcription, DNA replication, and DNA repair. The KDM4 family of Jumonj domain histone demethylases specifically target di- and tri-methylated lysine 9 on histone H3 (H3K9me3), removing a modification central to defining heterochromatin and gene repression. KDM4 enzymes are generally over-expressed in cancers, making them compelling targets for study and therapeutic inhibition. One of these family members, KDM4B, is especially interesting due to its regulation by multiple cellular stimuli, including DNA damage, steroid hormones, and hypoxia. In this review, we discuss what is known about the regulation of KDM4B in response to the cellular environment, and how this context-dependent expression may be translated into specific biological consequences in cancer and reproductive biology.
Highlights
Once thought to be too chemically stable to be enzymatically reversed, methyllysine residues are recognized as dynamic components of the histone code [1,2]
We discuss what is known about the regulation of KDM4B in response to the cellular environment, and how this context-dependent expression may be translated into specific biological consequences in cancer and reproductive biology
The characterization of LSD1 (KDM1A) as the first histone demethylase in 2004 was quickly followed by the discovery that the Jumonji-domain family of genes constitutes a diverse group of histone demethylases capable of reversing many of the known methyllysine residues in histones [3,4,5,6]
Summary
Once thought to be too chemically stable to be enzymatically reversed, methyllysine residues are recognized as dynamic components of the histone code [1,2]. The founding gene Jumonji, named for the cruciform neural plate defect caused by genetic deletion in mice, contains a domain similar to the transcriptional co-repressor RBP2 ( known as JARID1A) [7,8]. By sequence comparison, this C-terminal portion of the Jumonji domain (JmjC) was shown to be a member of the large and diverse superfamily of non-heme iron-dependent dioxygenases [8,9]. JmjC-KDMs, we direct residues necessary to coordinate yet comprehensive functions as a survey co-repressor the polycomb silencing the reader several reviewssurvey [1,9,10]. Its diverse expression patterns in several tissues and pathological states
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