期刊
CELL REPORTS
卷 12, 期 4, 页码 562-572出版社
CELL PRESS
DOI: 10.1016/j.celrep.2015.06.053
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类别
资金
- Wellcome Trust [081385, 091911]
- Micron advance imaging initiative (Wellcome Trust) [103768]
- Grants-in-Aid for Scientific Research [25503004] Funding Source: KAKEN
X-chromosome inactivation is the process that evolved in mammals to equalize levels of X-linked gene expression in XX females relative to XY males. Silencing of a single X chromosome in female cells is mediated by the non-coding RNA Xist. Although progress has been made toward identifying factors that function in the maintenance of X inactivation, the primary silencing factors are largely undefined. We developed an shRNA screening strategy to produce a ranked list of candidate primary silencing factors. Validation experiments performed on several of the top hits identified the SPOC domain RNA binding proteins Rbm15 and Spen and Wtap, a component of the m6A RNA methyltransferase complex, as playing an important role in the establishment of Xist-mediated silencing. Localization analysis using super-resolution 3D-SIM microscopy demonstrates that these factors co-localize with Xist RNA within the nuclear matrix subcompartment, consistent with a direct interaction.
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