title: Histone demethylation by a family of JmjC domain-containing proteins.
abstract: Covalent modification of histones has an important role in regulating chromatin dynamics and transcription. Whereas most covalent histone modifications are reversible, until recently it was unknown whether methyl groups could be actively removed from histones. Using a biochemical assay coupled with chromatography, we have purified a novel JmjC domain-containing protein, JHDM1 (JmjC domain-containing histone demethylase 1), that specifically demethylates histone H3 at lysine 36 (H3-K36). In the presence of Fe(ii) and alpha-ketoglutarate, JHDM1 demethylates H3-methyl-K36 and generates formaldehyde and succinate. Overexpression of JHDM1 reduced the level of dimethyl-H3-K36 (H3K36me2) in vivo. The demethylase activity of the JmjC domain-containing proteins is conserved, as a JHDM1 homologue in Saccharomyces cerevisiae also has H3-K36 demethylase activity. Thus, we identify the JmjC domain as a novel demethylase signature motif and uncover a protein demethylation mechanism that is conserved from yeast to human.
authors.affiliation: Howard Hughes Medical Institute, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.
authors.forename: Yu-ichi
authors.initials: Y
authors.lastname: Tsukada
authors.forename: Jia
authors.initials: J
authors.lastname: Fang
authors.forename: Hediye
authors.initials: H
authors.lastname: Erdjument-Bromage
authors.forename: Maria E
authors.initials: ME
authors.lastname: Warren
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Borchers
authors.forename: Paul
authors.initials: P
authors.lastname: Tempst
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D020816:Amino Acid Motifs; D002457:Cell Extracts; D017124:Conserved Sequence; D044783:F-Box Proteins; D005557:Formaldehyde / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases; D008745:Methylation; D010089:Oxidoreductases, N-Demethylating / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae; D013379:Substrate Specificity; D019802:Succinic Acid / Q000378:metabolism
chemical_list: D002457:Cell Extracts; D044783:F-Box Proteins; D006657:Histones; D005557:Formaldehyde; D019802:Succinic Acid; D056484:Jumonji Domain-Containing Histone Demethylases; C534524:KDM2A protein, human; D010089:Oxidoreductases, N-Demethylating