title: Crystal structure of the N-terminal region of human Ash2L shows a winged-helix motif involved in DNA binding.
abstract: Ash2L is a core component of the MLL family histone methyltransferases and has an important role in regulating the methylation of histone H3 on lysine 4. Here, we report the crystal structure of the N-terminal domain of Ash2L and reveal a new function of Ash2L. The structure shows that Ash2L contains an atypical PHD finger that does not have histone tail-binding activity. Unexpectedly, the structure shows a previously unrecognized winged-helix motif that directly binds to DNA. The DNA-binding-deficient mutants of Ash2L reduced Ash2L localization to the HOX locus. Strikingly, a single mutation in Ash2L(WH) (K131A) breaks the chromatin domain boundary, suggesting that Ash2L also has a role in chromosome demarcation.
authors.affiliation: Howard Hughes Medical Institute, 1150 West, Medical Center Drive, Ann Arbor, Michigan 48109, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Bingbing
authors.initials: B
authors.lastname: Wan
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Cao
authors.forename: Yuting
authors.initials: Y
authors.lastname: Yang
authors.forename: Angeline
authors.initials: A
authors.lastname: Protacio
authors.forename: Yali
authors.initials: Y
authors.lastname: Dou
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002843:Chromatin / Q000378:metabolism; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D056426:Genetic Loci; D006657:Histones / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051540:Winged-Helix Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C485622:ASH2L protein, human; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D014157:Transcription Factors; D051540:Winged-Helix Transcription Factors; D004247:DNA