title: RYBP represses endogenous retroviruses and preimplantation- and germ line-specific genes in mouse embryonic stem cells.
abstract: Polycomb repressive complexes (PRCs) are important chromatin regulators of embryonic stem (ES) cell function. RYBP binds Polycomb H2A monoubiquitin ligases Ring1A and Ring1B and has been suggested to assist PRC localization to their targets. Moreover, constitutive inactivation of RYBP precludes ES cell formation. Using ES cells conditionally deficient in RYBP, we found that RYBP is not required for maintenance of the ES cell state, although mutant cells differentiate abnormally. Genome-wide chromatin association studies showed RYBP binding to promoters of Polycomb targets, although its presence is dispensable for gene repression. We discovered, using Eed-knockout (KO) ES cells, that RYBP binding to promoters was independent of H3K27me3. However, recruiting of PRC1 subunits Ring1B and Mel18 to their targets was not altered in the absence of RYBP. In contrast, we have found that RYBP efficiently represses endogenous retroviruses (murine endogenous retrovirus [MuERV] class) and preimplantation (including zygotic genome activation stage)- and germ line-specific genes. These observations support a selective repressor activity for RYBP that is dispensable for Polycomb function in the ES cell state. Also, they suggest a role for RYBP in epigenetic resetting during preimplantation development through repression of germ line genes and PcG targets before formation of pluripotent epiblast cells.
authors.affiliation: Immunoepigenetics, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan. mvidal@cib.csic.es
authors.forename: Kaori
authors.initials: K
authors.lastname: Hisada
authors.forename: Carmen
authors.initials: C
authors.lastname: Sánchez
authors.forename: Takaho A
authors.initials: TA
authors.lastname: Endo
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Endoh
authors.forename: Mónica
authors.initials: M
authors.lastname: Román-Trufero
authors.forename: Jafar
authors.initials: J
authors.lastname: Sharif
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.forename: Miguel
authors.initials: M
authors.lastname: Vidal
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000821:virology*; D020077:Endogenous Retroviruses / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism; D054884:Host-Pathogen Interactions; D051379:Mice; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D012097:Repressor Proteins; C120616:Rybp protein, mouse