Abstract
The SAGA (Spt-Ada-Gcn5 acetyltransferase) complex is an important chromatin modifying complex that can both acetylate and deubiquitinate histones. Sgf29 is a novel component of the SAGA complex. Here, we report the crystal structures of the tandem Tudor domains of Saccharomyces cerevisiae and human Sgf29 and their complexes with H3K4me2 and H3K4me3 peptides, respectively, and show that Sgf29 selectively binds H3K4me2/3 marks. Our crystal structures reveal that Sgf29 harbours unique tandem Tudor domains in its C-terminus. The tandem Tudor domains in Sgf29 tightly pack against each other face-to-face with each Tudor domain harbouring a negatively charged pocket accommodating the first residue alanine and methylated K4 residue of histone H3, respectively. The H3A1 and K4me3 binding pockets and the limited binding cleft length between these two binding pockets are the structural determinants in conferring the ability of Sgf29 to selectively recognize H3K4me2/3. Our in vitro and in vivo functional assays show that Sgf29 recognizes methylated H3K4 to recruit the SAGA complex to its targets sites and mediates histone H3 acetylation, underscoring the importance of Sgf29 in gene regulation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Acetylation
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Acetyltransferases / chemistry*
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Acetyltransferases / genetics
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Acetyltransferases / metabolism*
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Amino Acid Sequence
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Blotting, Western
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Chromatin Immunoprecipitation
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Gene Expression Regulation*
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Histone Acetyltransferases / chemistry*
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Histone Acetyltransferases / genetics
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Histone Acetyltransferases / metabolism*
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Histones / metabolism*
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Humans
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Molecular Sequence Data
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Peptide Fragments
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Protein Processing, Post-Translational
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Protein Structure, Tertiary
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RNA, Messenger / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins / chemistry*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
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Sequence Homology, Amino Acid
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Trans-Activators / genetics
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Trans-Activators / metabolism*
Substances
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Histones
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Peptide Fragments
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RNA, Messenger
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SAGA complex, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Trans-Activators
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Acetyltransferases
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Sgf29 protein, human
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Histone Acetyltransferases
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Sgf29 protein, S cerevisiae