title: Coordinated methyl-lysine erasure: structural and functional linkage of a Jumonji demethylase domain and a reader domain.
abstract: Both components of chromatin (DNA and histones) are subjected to dynamic postsynthetic 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 lysine-specific demethylase 1 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.
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA.
authors.forename: Anup K
authors.initials: AK
authors.lastname: Upadhyay
authors.forename: John R
authors.initials: JR
authors.lastname: Horton
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cheng
mesh_terms: D044503:5-Methylcytosine / Q000737:chemistry / Q000378:metabolism / Q000031:analogs & derivatives; D003596:Cytosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D056466:Histone Demethylases / Q000737:chemistry / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000737:chemistry* / Q000378:metabolism; D008239:Lysine / Q000737:chemistry* / Q000378:metabolism; D008745:Methylation; D013329:Structure-Activity Relationship
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D004247:DNA; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; D008239:Lysine