title: Human but not yeast CHD1 binds directly and selectively to histone H3 methylated at lysine 4 via its tandem chromodomains.
abstract: Defining the protein factors that directly recognize post-translational, covalent histone modifications is essential toward understanding the impact of these chromatin "marks" on gene regulation. In the current study, we identify human CHD1, an ATP-dependent chromatin remodeling protein, as a factor that directly and selectively recognizes histone H3 methylated on lysine 4. In vitro binding studies identified that CHD1 recognizes di- and trimethyl H3K4 with a dissociation constant (Kd) of approximately 5 microm, whereas monomethyl H3K4 binds CHD1 with a 3-fold lower affinity. Surprisingly, human CHD1 binds to methylated H3K4 in a manner that requires both of its tandem chromodomains. In vitro analyses demonstrate that unlike human CHD1, yeast Chd1 does not bind methylated H3K4. Our findings indicate that yeast and human CHD1 have diverged in their ability to discriminate covalently modified histones and link histone modification-recognition and non-covalent chromatin remodeling activities within a single human protein.
authors.affiliation: Howard Hughes Medical Institute and Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Sims
authors.forename: Chi-Fu
authors.initials: CF
authors.lastname: Chen
authors.forename: Helena
authors.initials: H
authors.lastname: Santos-Rosa
authors.forename: Tony
authors.initials: T
authors.lastname: Kouzarides
authors.forename: Smita S
authors.initials: SS
authors.lastname: Patel
authors.forename: Danny
authors.initials: D
authors.lastname: Reinberg
mesh_terms: D000595:Amino Acid Sequence; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008969:Molecular Sequence Data; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: C489847:CHD1 protein, S cerevisiae; D004268:DNA-Binding Proteins; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D004265:DNA Helicases; C080359:CHD1 protein, human; D008239:Lysine