Coordinated Methyl-lysine Erasure: Structural and Functional Linkage of a Jumonji demethylasedomain and a Reader domain

• Type of Material: Article
• Authors: Anup K. Upadhyay, Emory University; John Horton, Emory University; Xing Zhang, Emory University; Xiaodong Cheng, Emory University
• Language: English
• Date: 2011-12
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.sbi.2011.08.003
• Title of Journal or Parent Work: Current Opinion in Structural Biology
• ISSN: 0959-440X
• Volume: 21
• Issue: 6
• Start Page: 750
• End Page: 760
• Grant/Funding Information: X.C. is a Georgia Research Alliance Eminent Scholar.; The work in the Cheng laboratory was supported by grants GM068680 and GM049245 from the National Institutes of Health.
• Research Categories: Chemistry, Biochemistry

Abstract

Both components of chromatin (DNA and histones) are subjected to dynamic post-synthetic covalent modifications. Dynamic histone lysine methylation involves the activities of modifying enzymes (writers), enzymes removing modifications (erasers), and readers of the epigenetic code. Known histone lysine demethylases include flavin-dependent monoamine oxidase LSD1 and α-ketoglutarate-Fe(II)-dependent dioxygenases containing Jumonji domains. Importantly, the Jumonji domain often associates with at least one additional recognizable domain (reader) within the same polypeptide that detects the methylation status of histones and/or DNA. Here, we summarize recent developments in characterizing structural and functional properties of various histone lysine demethylases, with emphasis on a mechanism of crosstalk between a Jumonji domain and its associated reader module(s). We further discuss the role of recently identified Tet1 enzyme in oxidizing 5-methylcytosine to 5-hydroxymethylcytosine in DNA.