title: Polycomb repressive complex 1 controls uterine decidualization.
abstract: Uterine stromal cell decidualization is an essential part of the reproductive process. Decidual tissue development requires a highly regulated control of the extracellular tissue remodeling; however the mechanism of this regulation remains unknown. Through systematic expression studies, we detected that Cbx4/2, Rybp, and Ring1B [components of polycomb repressive complex 1 (PRC1)] are predominantly utilized in antimesometrial decidualization with polyploidy. Immunofluorescence analyses revealed that PRC1 members are co-localized with its functional histone modifier H2AK119ub1 (mono ubiquitination of histone-H2A at lysine-119) in polyploid cell. A potent small-molecule inhibitor of Ring1A/B E3-ubiquitin ligase or siRNA-mediated suppression of Cbx4 caused inhibition of H2AK119ub1, in conjunction with perturbation of decidualization and polyploidy development, suggesting a role for Cbx4/Ring1B-containing PRC1 in these processes. Analyses of genetic signatures by RNA-seq studies showed that the inhibition of PRC1 function affects 238 genes (154 up and 84 down) during decidualization. Functional enrichment analyses identified that about 38% genes primarily involved in extracellular processes are specifically targeted by PRC1. Furthermore, ~15% of upregulated genes exhibited a significant overlap with the upregulated Bmp2 null-induced genes in mice. Overall, Cbx4/Ring1B-containing PRC1 controls decidualization via regulation of extracellular gene remodeling functions and sheds new insights into underlying molecular mechanism(s) through transcriptional repression regulation.
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.|Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.|Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Bian
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.|Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.|Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.|Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.|Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kartashov
authors.affiliation: Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.|Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Anil G
authors.initials: AG
authors.lastname: Jegga
authors.affiliation: Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.|Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.|Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Artem
authors.initials: A
authors.lastname: Barski
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.|Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.|Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Das
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics; D002478:Cells, Cultured; D003656:Decidua / Q000473:pathology*; D063185:Epigenetic Repression; D005260:Female; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D063146:Polycomb-Group Proteins / Q000378:metabolism*; D011123:Polyploidy; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D017154:Stromal Cells / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D014599:Uterus / Q000473:pathology*
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D006657:Histones; D063146:Polycomb-Group Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C120616:Rybp protein, mouse; D063150:Polycomb Repressive Complex 1; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; C570504:Cbx4 protein, mouse