title: Cbx2 targets PRC1 to constitutive heterochromatin in mouse zygotes in a parent-of-origin-dependent manner.
abstract: Polycomb repressive complexes PRC1 and PRC2 regulate expression of genes involved in proliferation and development. In mouse early embryos, however, canonical PRC1 localizes to paternal pericentric heterochromatin (pat-PCH), where it represses transcription of major satellite repeats. In contrast, maternal PCH (mat-PCH) is enriched for H3 lysine 9 tri-methylation (H3K9me3) and Hp1β. How PRC1 is targeted to pat-PCH, yet excluded from mat-PCH, has remained elusive. Here, we identify a PRC1 targeting mechanism that relies on Cbx2 and Hp1β. Cbx2 directs catalytically active PRC1 to PCH via its chromodomain (CD(Cbx2)) and neighboring AT-hook (AT(Cbx2)) binding to H3K27me3 and AT-rich major satellites, respectively. CD(Cbx2) prevents AT(Cbx2) from interacting with DNA at PCH marked by H3K9me3 and Hp1β. Loss-of-function studies show that Hp1β and not H3K9me3 prevents PRC1 targeting to mat-PCH. Our findings indicate that CD(Cbx2) and AT(Cbx2) separated by a short linker function together to integrate H3K9me3/HP1 and H3K27me3 states.
authors: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors: Mathieu
authors: M
authors: Tardat
authors: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Faculty of Sciences, University of Basel, 4056 Basel, Switzerland.
authors: Mareike
authors: M
authors: Albert
authors: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Faculty of Sciences, University of Basel, 4056 Basel, Switzerland.
authors: Rico
authors: R
authors: Kunzmann
authors: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors: Zichuan
authors: Z
authors: Liu
authors: Princess Margaret Cancer Centre and Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors: Lilia
authors: L
authors: Kaustov
authors: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors: Raphael
authors: R
authors: Thierry
authors: Princess Margaret Cancer Centre and Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors: Shili
authors: S
authors: Duan
authors: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Faculty of Sciences, University of Basel, 4056 Basel, Switzerland.
authors: Urszula
authors: U
authors: Brykczynska
authors: Princess Margaret Cancer Centre and Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A8, Canada; Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
authors: Cheryl H
authors: CH
authors: Arrowsmith
authors: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Faculty of Sciences, University of Basel, 4056 Basel, Switzerland. Electronic address: antoine.peters@fmi.ch.
authors: Antoine H F M
authors: AH
authors: Peters
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002503:Centromere; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006570:Heterochromatin / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D040582:Inheritance Patterns; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D063150:Polycomb Repressive Complex 1 / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D015053:Zygote / Q000254:growth & development / Q000378:metabolism*
chemical_list: C096188:Cbx1 protein, mouse; C570426:Cbx2 protein, mouse; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D006657:Histones; D012097:Repressor Proteins; C498700:Suv39h1 protein, mouse; D008780:Methyltransferases; D063150:Polycomb Repressive Complex 1