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Erasing the Methyl Mark: Histone Demethylases at the Center of Cellular Differentiation and Disease

Overview
Journal Genes Dev
Specialty Molecular Biology
Date 2008 May 3
PMID 18451103
Citations 326
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Abstract

The enzymes catalyzing lysine and arginine methylation of histones are essential for maintaining transcriptional programs and determining cell fate and identity. Until recently, histone methylation was regarded irreversible. However, within the last few years, several families of histone demethylases erasing methyl marks associated with gene repression or activation have been identified, underscoring the plasticity and dynamic nature of histone methylation. Recent discoveries have revealed that histone demethylases take part in large multiprotein complexes synergizing with histone deacetylases, histone methyltransferases, and nuclear receptors to control developmental and transcriptional programs. Here we review the emerging biochemical and biological functions of the histone demethylases and discuss their potential involvement in human diseases, including cancer.

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References
1.
Kouzarides T . Chromatin modifications and their function. Cell. 2007; 128(4):693-705. DOI: 10.1016/j.cell.2007.02.005. View

2.
Forneris F, Binda C, DallAglio A, Fraaije M, Battaglioli E, Mattevi A . A highly specific mechanism of histone H3-K4 recognition by histone demethylase LSD1. J Biol Chem. 2006; 281(46):35289-95. DOI: 10.1074/jbc.M607411200. View

3.
Valk-Lingbeek M, Bruggeman S, van Lohuizen M . Stem cells and cancer; the polycomb connection. Cell. 2004; 118(4):409-18. DOI: 10.1016/j.cell.2004.08.005. View

4.
Chinenov Y . A second catalytic domain in the Elp3 histone acetyltransferases: a candidate for histone demethylase activity?. Trends Biochem Sci. 2002; 27(3):115-7. DOI: 10.1016/s0968-0004(02)02058-3. View

5.
Agger K, Cloos P, Christensen J, Pasini D, Rose S, Rappsilber J . UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature. 2007; 449(7163):731-4. DOI: 10.1038/nature06145. View