期刊
EMBO REPORTS
卷 22, 期 3, 页码 -出版社
WILEY
DOI: 10.15252/embr.202051989
关键词
embryonic stem cells; heterochromatin; polycomb; X inactivation
资金
- Fundacao para a Ciencia e Tecnologia [PTDC/BIA-MOL/29320/2017, CEECUIND/01234/207, SFRH/BD/137099/2018]
- ERC [671027]
- Sir Henry Wellcome Postdoctoral Fellowship
- Japan Society for the Promotion of Science KAKENHI [JP17KK0143, JP20K06484, JP19H04970, JP19H03158, JP20H05393, JP17K17719, JP18H05534, JP18H05527, JP20H00456, JP17H01417]
- Japan Science and Technology Agency (JST) [JPMJCR16G1, JPMJPR2026, JPMJER1901]
- Novo Nordisk Foundation Center for Stem Cell Biology (Novo Nordisk Foundation) [NNF17CC0027852]
- Projekt DEAL
- European Research Council (ERC) [671027] Funding Source: European Research Council (ERC)
- Fundação para a Ciência e a Tecnologia [PTDC/BIA-MOL/29320/2017, SFRH/BD/137099/2018] Funding Source: FCT
This study revealed the simultaneous accumulation of H3K27me3 and H4K20me1 during XCI, with distinct genomic distributions, using a genetically encoded intracellular antibody specific to H3K27me3. Additionally, the use of a Xist repeat mutant showed that H4K20me1 is dispensable for initiating gene silencing, providing insights into the dynamics of XCI and chromatin modifications during this process.
During X chromosome inactivation (XCI), in female placental mammals, gene silencing is initiated by the Xist long non-coding RNA. Xist accumulation at the X leads to enrichment of specific chromatin marks, including PRC2-dependent H3K27me3 and SETD8-dependent H4K20me1. However, the dynamics of this process in relation to Xist RNA accumulation remains unknown as is the involvement of H4K20me1 in initiating gene silencing. To follow XCI dynamics in living cells, we developed a genetically encoded, H3K27me3-specific intracellular antibody or H3K27me3-mintbody. By combining live-cell imaging of H3K27me3, H4K20me1, the X chromosome and Xist RNA, with ChIP-seq analysis we uncover concurrent accumulation of both marks during XCI, albeit with distinct genomic distributions. Furthermore, using a Xist B and C repeat mutant, which still shows gene silencing on the X but not H3K27me3 deposition, we also find a complete lack of H4K20me1 enrichment. This demonstrates that H4K20me1 is dispensable for the initiation of gene silencing, although it may have a role in the chromatin compaction that characterises facultative heterochromatin.
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