Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins.
Members of the heterochromatin protein 1 (HP1) family are silencing nonhistone proteins. Here, we show that in P19 embryonal carcinoma (EC) nuclei, HP1 alpha, beta, and gamma form homo- and heteromers associated with nucleosomal core histones. In vitro, all three HP1s bind to tailed and tailless nucleosomes and specifically interact with the histone-fold of histone H3. Furthermore, HP1alpha interacts with the linker histone H1. HP1alpha binds to H3 and H1 through its chromodomain (CD) and hinge region, respectively. Interestingly, the Polycomb (Pc1/M33) CD also interacts with H3, and HP1alpha and Pc1/M33 binding to H3 is severely impaired by CD mutations known to abrogate HP1 and Polycomb silencing in Drosophila. These results define a novel function for the conserved CD and suggest that HP1 self-association and histone binding may play a crucial role in HP1-mediated heterochromatin assembly.
Nielsen
A L
AL
Department of Molecular and Structural Biology and Institute of Human Genetics, Aarhus University, C. F. Mollersalle 130, DK-8000 C, Aarhus, Denmark.
Oulad-Abdelghani
M
M
Ortiz
J A
JA
Remboutsika
E
E
Chambon
P
P
Losson
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D004330:Drosophila; D054278:Embryonal Carcinoma Stem Cells; D000939:Epitopes / Q000235:genetics; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D014411:Neoplastic Stem Cells; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D009842:Oligopeptides; D010455:Peptides / Q000235:genetics; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
C000715594:CBX5 protein, human; C570426:Cbx2 protein, mouse; D002868:Chromosomal Proteins, Non-Histone; D000939:Epitopes; D006570:Heterochromatin; D006657:Histones; D009707:Nucleosomes; D009842:Oligopeptides; D010455:Peptides; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D000090266:Chromobox Protein Homolog 5; C085706:FLAG peptide; D063150:Polycomb Repressive Complex 1