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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs*
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Amino Acid Sequence
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Chromatin / metabolism
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Crystallography, X-Ray
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DNA / chemistry
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DNA / metabolism
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Genetic Loci
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Histones / metabolism
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Humans
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Models, Molecular
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Molecular Sequence Data
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Mutation
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Nuclear Proteins / chemistry*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Protein Structure, Tertiary
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Transcription Factors / chemistry*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Winged-Helix Transcription Factors / chemistry*
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Winged-Helix Transcription Factors / genetics
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Winged-Helix Transcription Factors / metabolism
Substances
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ASH2L protein, human
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Chromatin
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DNA-Binding Proteins
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Histones
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Nuclear Proteins
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Transcription Factors
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Winged-Helix Transcription Factors
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DNA