Histone Demethylase

Histone Demethylase

There are two classes of histone demethylases: the amine-oxidase type Lysine specific demethylases (LSD1) and LSD2 and a whole group of so-called JmJC-domain containing histone demethylases.

An Overview of Histone Demethylase

Histone methylation is an important form of epigenetic modification and has important roles in regulating gene expression and forms part of the epigenetic memory system that regulates cell fate and identity. Histone demethylase is one of the two enzymes involved in histone methylation, and the other is methyltransferase. Comparing the two enzymes, demethylases remove the methyl groups, and sometimes can remove other proteins. Histone demethylases is not only the methylation site of histone tails, but also interacts with the methylation sites of non histone proteins.

Major Types of Histone Demethylase

There are two classes of histone demethylases: the amine-oxidase type Lysine specific demethylases 1 (LSD1) and LSD2 and a whole group of so-called Jumonji C (JmJC)-domain containing histone demethylases (JHDMs). The structure of LSD1 consists of an Nterminal SWIRM domain, and an amine oxidase domain split into two halves, consisting of a substrate-binding half and an flavin adenine dinucleotide (FAD) binding half, which come together to form a globular domain, and the active site of the enzyme is located in between these two halves two long. The Jumonji domain protein 2 (JMJD2) family is the first of the JmJC proteins. The JmjC through an oxidative reaction that requires iron Fe(II) and α-ketoglutarate (αKG) as cofactors. Unlike LSD1, which can only remove mono- and dimethyl lysine modifications, the JHDMs can remove all three histone lysine-methylation states.

Inhibition of Histone Demethylase

Contains three major inhibitors: , and ). Several JmjC-domain-containing proteins have been functionally implicated in inherited disease and cancer, indicating that these enzymes have important roles in cellular homeostasis and might be suitable targets for therapeutic intervention.

References:

Tsukada Y. (2006). Histone demethylation by a family of JmjC domain-containing proteins. Nature, 439(16), 811-816.

RobertJ.Klose. (2006). JmjC-domain-containing proteins and histone demethylation. Nature Reviews Genetics, 7,715-727.

Mosammaparast N. (2010). Reversal of Histone Methylation: Biochemical and Molecular Mechanisms of Histone Demethylases. Annual Review of Biochemistry, 79(1), 155-179.

Grant S. (2009). Differential activation of dual signaling responses by human H1 and H2 histamine receptors. Clin Cancer Res,15(23): 7111 –7113.

KH Chang. (2011). Inhibition of Histone Demethylases by 4-Carboxy-2,2’-Bipyridyl Compounds. Chemmedchem,6(5): 759–764.

Y Shi. (2004). Histone Demethylation Mediated by the Nuclear Amine Oxidase Homolog LSD1. Cell,119: 941–953.

Products for Histone Demethylase

Price Inquiry
© 2017 MuseChem - A division of ArrakisTek Inc. All Rights Reserved.