Cbx2 targets PRC1 to constitutive heterochromatin in mouse zygotes in a parent-of-origin-dependent manner

Mol Cell. 2015 Apr 2;58(1):157-71. doi: 10.1016/j.molcel.2015.02.013. Epub 2015 Mar 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Centromere
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation, Developmental*
  • Heterochromatin / chemistry
  • Heterochromatin / metabolism*
  • Histones / genetics
  • Histones / metabolism
  • Inheritance Patterns
  • Male
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Polycomb Repressive Complex 1 / genetics*
  • Polycomb Repressive Complex 1 / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Sequence Alignment
  • Signal Transduction
  • Zygote / growth & development
  • Zygote / metabolism*


  • Cbx1 protein, mouse
  • Cbx2 protein, mouse
  • Chromosomal Proteins, Non-Histone
  • Heterochromatin
  • Histones
  • Repressor Proteins
  • Suv39h1 protein, mouse
  • Methyltransferases
  • Polycomb Repressive Complex 1