title: Interaction of HP1 and Brg1/Brm with the globular domain of histone H3 is required for HP1-mediated repression.
abstract: The heterochromatin-enriched HP1 proteins play a critical role in regulation of transcription. These proteins contain two related domains known as the chromo- and the chromoshadow-domain. The chromo-domain binds histone H3 tails methylated on lysine 9. However, in vivo and in vitro experiments have shown that the affinity of HP1 proteins to native methylated chromatin is relatively poor and that the opening of chromatin occurring during DNA replication facilitates their binding to nucleosomes. These observations prompted us to investigate whether HP1 proteins have additional histone binding activities, envisioning also affinity for regions potentially occluded by the nucleosome structure. We find that the chromoshadow-domain interacts with histone H3 in a region located partially inside the nucleosomal barrel at the entry/exit point of the nucleosome. Interestingly, this region is also contacted by the catalytic subunits of the human SWI/SNF complex. In vitro, efficient SWI/SNF remodeling requires this contact and is inhibited in the presence of HP1 proteins. The antagonism between SWI/SNF and HP1 proteins is also observed in vivo on a series of interferon-regulated genes. Finally, we show that SWI/SNF activity favors loading of HP1 proteins to chromatin both in vivo and in vitro. Altogether, our data suggest that HP1 chromoshadow-domains can benefit from the opening of nucleosomal structures to bind chromatin and that HP1 proteins use this property to detect and arrest unwanted chromatin remodeling.
authors.affiliation: Institut Pasteur, Département de Biologie du Développement, Unité de Recherche Associée URA2578 du Centre National de la Recherche Scientifique CNRS, Unité de Régulation Epigénétique, équipe AVENIR de l'Institut National de la Santé Et de la Recherche Médicale INSERM, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lavigne
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Eskeland
authors.forename: Saliha
authors.initials: S
authors.lastname: Azebi
authors.forename: Violaine
authors.initials: V
authors.lastname: Saint-André
authors.forename: Suk Min
authors.initials: SM
authors.lastname: Jang
authors.forename: Eric
authors.initials: E
authors.lastname: Batsché
authors.forename: Hua-Ying
authors.initials: HY
authors.lastname: Fan
authors.forename: Robert E
authors.initials: RE
authors.lastname: Kingston
authors.forename: Axel
authors.initials: A
authors.lastname: Imhof
authors.forename: Christian
authors.initials: C
authors.lastname: Muchardt
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism*; D017931:DNA Primers; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D034622:RNA Interference; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D017931:DNA Primers; D006570:Heterochromatin; D006657:Histones; D009687:Nuclear Proteins; C084011:SMARCA2 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases