The Polycomb group protein Cbx6 is an essential regulator of embryonic stem cell identity

Polycomb group (PcG) proteins are transcriptional repressors that control cell identity and development. In mammals, at least five different Cbx prorteins are believed to associate with the core Polycomb repressive complex 1 (PRC1), Cbx6 and Cbx7 are the more expressed in embryonic stem (ES) cells,...

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Detalhes bibliográficos
Autor: Santanach Buxaderas, Alexandra
Formato: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2016
País:España
Recursos:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/482208
Acesso em linha:http://hdl.handle.net/10803/482208
Access Level:acceso abierto
Palavra-chave:Embryonic stem cells
Polycomb
Chromobox domain
Pluripotency
Signalling pathway
Cèl·lules mare embrionàries
Domini chromobox
Via de senyalització
Pluripotència
576
Descrição
Resumo:Polycomb group (PcG) proteins are transcriptional repressors that control cell identity and development. In mammals, at least five different Cbx prorteins are believed to associate with the core Polycomb repressive complex 1 (PRC1), Cbx6 and Cbx7 are the more expressed in embryonic stem (ES) cells, yet little is known about the function of Cbx6 in these cells. Here we have characterized the function of Cbx6 in ES cell pluripotency and differentiation. We show that Cbx6 is an essential regulator of ES cell identity, since ablation of Cbx6 function destabilizes the pluripotency network, trough a perturbation of the Wnt and Mapk signalling pathways, and triggers differentiation towards the ectoderm fate. Cbx6 mass spectrometry data and genome-wide chromatin occupancy unveils that Cbx6 is unequivocally linked to the canonical PRC1 (cPRC1) complex, however, contrary to expectations, our results indicate that Cbx6 also has a non-canonical PRC1 function. Taken together, our findings reveal that Cbx6 is an essential component for ES cell biology, and contributes to the structural and functional complexity of the PRC1 complex.