Journal
EMBO REPORTS
Volume 20, Issue 10, Pages -Publisher
WILEY
DOI: 10.15252/embr.201948019
Keywords
chromatin; PRC1; PRC2; X-chromosome inactivation; Xist
Categories
Funding
- Fundacao para a Ciencia e Tecnologia (FCT) [PTDC/BEX-BCM/2612/2014, PTDC/BIA-MOL/29320/2017 IC DT, IF/00242/2014]
- ERC [ERC-ADG-2014 671027]
- Sir Henry Wellcome Postdoctoral Fellowship
- Scleroderma Research Foundation
- US National Institutes of Health [NIH P50-HG007735]
- Fundacao para a Ciencia e a Tecnologia (FCT)/Ministerio da Ciencia, Tecnologia e Ensino Superior (MCTES) through Fundos do Orcamento de Estado [UID/BIM/50005/2019]
- Fundação para a Ciência e a Tecnologia [PTDC/BIA-MOL/29320/2017, PTDC/BEX-BCM/2612/2014] Funding Source: FCT
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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-inducible mutants at the endogenous locus in male mouse embryonic stem (ES) cells, we dissect the role of the conserved A-B-C-F repeats in the initiation of XCI. We find that transcriptional silencing can be largely uncoupled from Polycomb repressive complex 1 and complex 2 (PRC1/2) recruitment, which requires B and C repeats. Xist Delta B+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 Delta B+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.
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