title: DYRK1A phoshorylates histone H3 to differentially regulate the binding of HP1 isoforms and antagonize HP1-mediated transcriptional repression.
abstract: Heterochromatin protein 1 (HP1) proteins are chromatin-bound transcriptional regulators. While their chromodomain binds histone H3 methylated on lysine 9, their chromoshadow domain associates with the H3 histone fold in a region involved in chromatin remodeling. Here, we show that phosphorylation at histone H3 threonine 45 and serine 57 within this latter region differentially affects binding of the three mammalian HP1 isoforms HP1α, HP1β and HP1γ. Both phosphorylation events are dependent on the activity of the DYRK1A kinase that antagonizes HP1-mediated transcriptional repression and participates in abnormal activation of cytokine genes in Down's syndrome-associated megakaryoblastic leukemia.
authors.affiliation: Institut Pasteur, Dpt Biologie du Développement et Cellules Souches Unité de Régulation Epigénétique, Paris, France URA2578, CNRS, Paris, France Sorbonne Universités UPMC Univ Paris06, IFD, Paris cedex05, France.
authors.forename: Suk Min
authors.initials: SM
authors.lastname: Jang
authors.affiliation: Institut Pasteur, Dpt Biologie du Développement et Cellules Souches Unité de Régulation Epigénétique, Paris, France URA2578, CNRS, Paris, France Sorbonne Universités UPMC Univ Paris06, IFD, Paris cedex05, France.
authors.forename: Saliha
authors.initials: S
authors.lastname: Azebi
authors.affiliation: Institut Pasteur, Dpt Génomes et Génétique, Plate-forme Transcriptome et Epigénome, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Soubigou
authors.affiliation: Institut Pasteur, Dpt Biologie du Développement et Cellules Souches Unité de Régulation Epigénétique, Paris, France URA2578, CNRS, Paris, France christian.muchardt@pasteur.fr.
authors.forename: Christian
authors.initials: C
authors.lastname: Muchardt
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000097603:Dyrk Kinases
chemical_list: D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases; C000715593:CBX1 protein, human; C000715594:CBX5 protein, human
keywords: chromatin silencing; cytokine; epigenetic; histone code; inflammation