Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease.

By P. Cloos, J. Christensen, K. Agger, K. Helin. Genes & Development, 2008

686 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9d6f619ca2b149727f4d17a58dee0c5a50f63a3e

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Citations in the corpus

Mutations of polycomb‐associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia (2009, background): “Inactivating somatic alterations of the UTX gene in various human cancers, including chronic and acute myeloid leukaemias, have just been reported [van Haaften, G., Dalgliesh, G.L., Davies, H., Chen, L., Bignell, G., Greenman, C., Edkins, S., Hardy, C., O’Meara, S., Teague, J., Butler, A., Hinton, J”
ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases (2016, neutral): “which erases the methyl mark [208].”
Ascorbic acid: Chemistry, biology and the treatment of cancer (2012, background): “The newly discovered histone demethylases containing Jumonji catalytic domains, which can demethylate trimethylated lysines, also belong to the Fe2+–2-oxoglutarate dioxygenase family [85].”
Deregulation of the Histone Lysine-Specific Demethylase 1 Is Involved in Human Hepatocellular Carcinoma (2019, background): “So far, approximately 50 different histone lysine methyltransferases (HKMTs) [15], 10 histone arginine methyltransferases (HRMTs) [15], and 30 histone demethylases (HDMs) [16] have been identified, but biological and physiological functions of these enzymes are still not fully clarified.”
Epigenetics in cancer. (2010, background): “In addition to histone methyltransferases, lysine specific-demethylases which work in coordination with HMTs to maintain global histone methylation patterns, are also implicated in cancer progression [96].”
A Functional Link between the Histone Demethylase PHF8 and the Transcription Factor ZNF711 in X-Linked Mental Retardation (2010, positive): “This protein family has 27 members, and several of these have recently been shown to be histone lysine demethylases playing important roles in development and differentiation (Cloos et al., 2008; Klose and Zhang, 2007; Lan et al., 2008).”
Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. (2010, background): “Histone demethylases are important for development and modulate the expression of the ESC master transcription factor Nanog (Cloos et al., 2008), so it is possible that Vc allows the reprogramming to run more smoothly by facilitating histone demethylation.”
Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers. (2010, background): “the JmJc domain-containing family of proteins that can remove methyl groups from arginine or lysine residues (Cloos et al., 2008).”
A chromatin-mediated reversible drug tolerant state in cancer cell subpopulations (2010, background): “KDM5A associates with histone deacetylases (HDACs) (Klose et al., 2007; reviewed in Cloos et al., 2008), and a yeast genetic screen to identify suppressors of DNA damage revealed the KDM5A ortholog Msc1, which was found to promote reduced histone H3K9/K14 acetylation (Ahmed et al., 2004).”