Exploring the role of Polycomb recruitment in Xist -mediated silencing of the X chromosome in ES cells
Exploring the role of Polycomb recruitment in Xist -mediated silencing of the X chromosome in ES cells
Abstract Xist RNA has been established as the master regulator of X-chromosome inactivation (XCI) in female eutherian mammals but its mechanism of action remains unclear. By creating novel Xist mutants at the endogenous locus in mouse embryonic stem (ES) cells, we dissect the role of the conserved A-B-C-F repeats. We find that transcriptional silencing can be largely uncoupled from Polycomb repressive complex 1 and 2 (PRC1/2) recruitment, which requires repeats B and C. Xist ΔB+C RNA specifically loses interaction with PCGF3/5 subunits of PRC1, while binding of other Xist partners is largely unaffected. However, a slight relaxation of transcriptional silencing in Xist ΔB+C indicates a role for PRC1/2 proteins in early stabilization of gene repression. Distinct modules within the Xist RNA are therefore involved in the convergence of independent chromatin modification and gene repression pathways. In this context, Polycomb recruitment seems to be of moderate relevance in the initiation of silencing.
Bousard Aur¨|lie、Pires Vanessa Borges、Syx Laur¨¨ne、Chang Howard Y.、Picard Christel、Heard Edith、Qi Yanyan、Rocha Sim?o Teixeira da、Raposo Ana Cl¨￠udia、?ylicz Jan Jakub
Mammalian Developmental Epigenetics Group, Institut Curie, PSL UniversityInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa||Instituto de Ci¨oncias Biom¨|dicas Abel Salazar, Universidade do PortoMammalian Developmental Epigenetics Group, Institut Curie, PSL UniversityCenter for Dynamic Personal Regulomes, Stanford University||Howard Hughes Medical Institute, Stanford UniversityMammalian Developmental Epigenetics Group, Institut Curie, PSL UniversityMammalian Developmental Epigenetics Group, Institut Curie, PSL UniversityCenter for Dynamic Personal Regulomes, Stanford UniversityMammalian Developmental Epigenetics Group, Institut Curie, PSL University||Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de LisboaInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de LisboaMammalian Developmental Epigenetics Group, Institut Curie, PSL University||University of Cambridge, Department of Physiology, Development and Neuroscience
遗传学分子生物学细胞生物学
Bousard Aur¨|lie,Pires Vanessa Borges,Syx Laur¨¨ne,Chang Howard Y.,Picard Christel,Heard Edith,Qi Yanyan,Rocha Sim?o Teixeira da,Raposo Ana Cl¨￠udia,?ylicz Jan Jakub.Exploring the role of Polycomb recruitment in Xist -mediated silencing of the X chromosome in ES cells[EB/OL].(2025-03-28)[2025-06-12].https://www.biorxiv.org/content/10.1101/495739.点此复制
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