title: A Phosphotyrosine Switch Controls the Association of Histone Mark Readers with Methylated Proteins.
abstract: Although histone post-translational modifications play a paramount role in controlling access to genetic information, our understanding of the precise mechanisms regulating chromatin signaling remains superficial. For instance, histone H3 trimethylated on lysine 9 (H3K9(me3)) favors the association of chromodomain proteins such as heterochromatin protein 1α (HP1α) with chromatin. However, HP1α and other such chromatin proteins are not covering all specific histone marks at all times. Thus, how are these reader-histone interactions regulated? We propose tyrosine phosphorylation within the aromatic cage of histone mark readers as a molecular switch that can either turn ON or OFF and even alter the specificity of reader-histone interactions. We have identified tyrosine phosphorylation events on the chromatin proteins HP1α and M-phase phosphoprotein 8 that regulate their association with methylated histones in vitro (synthetic peptides, calf thymus purified histones, and nucleosomes), but also in cells, thus controlling access to genetic information.
authors.affiliation: Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University , Paul O'Gorman Building, Medical School, Framlington Place, Newcastle upon Tyne, England NE2 4HH.
authors.forename: Bronwyn Kate
authors.initials: BK
authors.lastname: Irving-Hooper
authors.affiliation: Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University , Paul O'Gorman Building, Medical School, Framlington Place, Newcastle upon Tyne, England NE2 4HH.
authors.forename: Olivier
authors.initials: O
authors.lastname: Binda
mesh_terms: D000818:Animals; D002417:Cattle; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D019000:Phosphotyrosine / Q000235:genetics / Q000378:metabolism
chemical_list: C000715594:CBX5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; C547278:MPHOSPH8 protein, human; D009707:Nucleosomes; D010750:Phosphoproteins; D000090266:Chromobox Protein Homolog 5; D019000:Phosphotyrosine