title: The mammalian heterochromatin protein 1 binds diverse nuclear proteins through a common motif that targets the chromoshadow domain.
abstract: The HP1 proteins regulate epigenetic gene silencing by promoting and maintaining chromatin condensation. The HP1 chromodomain binds to methylated histone H3. More enigmatic is the chromoshadow domain (CSD), which mediates dimerization, transcription repression, and interaction with multiple nuclear proteins. Here we show that KAP-1, CAF-1 p150, and NIPBL carry a canonical amino acid motif, PxVxL, which binds directly to the CSD with high affinity. We also define a new class of variant PxVxL CSD-binding motifs in Sp100A, LBR, and ATRX. Both canonical and variant motifs recognize a similar surface of the CSD dimer as demonstrated by a panel of CSD mutants. These in vitro binding results were confirmed by the analysis of polypeptides found associated with nuclear HP1 complexes and we provide the first evidence of the NIPBL/delangin protein in human cells, a protein recently implicated in the developmental disorder, Cornelia de Lange syndrome. NIPBL is related to Nipped-B, a factor participating in gene activation by remote enhancers in Drosophila melanogaster. Thus, this spectrum of direct binding partners suggests an expanded role for HP1 as factor participating in promoter-enhancer communication, chromatin remodeling/assembly, and sub-nuclear compartmentalization.
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA. msl27@drexel.edu
authors.forename: Mark S
authors.initials: MS
authors.lastname: Lechner
authors.forename: David C
authors.initials: DC
authors.lastname: Schultz
authors.forename: Dmitri
authors.initials: D
authors.lastname: Negorev
authors.forename: Gerd G
authors.initials: GG
authors.lastname: Maul
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Rauscher
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D000090266:Chromobox Protein Homolog 5