title: Regulation of Methyllysine Readers through Phosphorylation.
abstract: Methyllysine post-translational modifications (PTMs) of histones create binding sites for evolutionarily conserved reader domains that link nuclear host proteins and chromatin-modifying complexes to specific genomic regions. In the context of these events, adjacent histone PTMs are capable of altering the binding activity of readers toward their target marks. This provides a mechanism of "combinatorial readout" of PTMs that can enhance, decrease, or eliminate the association of readers with chromatin. In this Perspective, we focus on recent studies describing the impact of dynamic phospho-serine/threonine/tyrosine marks on the interaction of methyllysine readers with histones, summarize mechanistic aspects of the phospho/methyl readout, and highlight the significance of crosstalk between these PTMs. We also demonstrate that in addition to inhibiting binding and serving as a true switch, promoting dissociation of the methyllysine readers from chromatin, the phospho/methyl combination can act together in a cooperative manner--thus adding a new layer of regulatory information that can be encoded in these dual histone PTMs.
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine , Aurora, Colorado 80045, United States.
authors.forename: Forest H
authors.initials: FH
authors.lastname: Andrews
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine , Aurora, Colorado 80045, United States.
authors.forename: Jovylyn
authors.initials: J
authors.lastname: Gatchalian
authors.affiliation: Department of Biochemistry & Biophysics, The University of North Carolina School of Medicine , Chapel Hill, North Carolina 27599, United States.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Krajewski
authors.affiliation: Department of Biochemistry & Biophysics, The University of North Carolina School of Medicine , Chapel Hill, North Carolina 27599, United States.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Strahl
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine , Aurora, Colorado 80045, United States.
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Kutateladze
mesh_terms: D001665:Binding Sites; D002843:Chromatin; D044127:Epigenesis, Genetic; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational
chemical_list: D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D008239:Lysine