Diverse factors are involved in maintaining X chromosome inactivation.

作者: K. M. Chan , H. Zhang , L. Malureanu , J. van Deursen , Z. Zhang

DOI: 10.1073/PNAS.1107616108

关键词: Small hairpin RNAGene silencingORC2GeneticsHeterochromatin protein 1Origin recognition complexX-inactivationX chromosomeBiologyRNA interference

摘要: X chromosome inactivation (XCI) is the most dramatic example of epigenetic silencing in eukaryotes. Once established, inactivated (Xi) remains silenced throughout subsequent cell divisions. Though initiation XCI has been studied extensively, protein factors involved Xi and maintenance are largely unknown. Here we report discovery a diverse set 32 proteins through genome-wide RNAi screen. In addition, describe mechanistic roles two proteins—origin recognition complex 2 (Orc2) heterochromatin 1 (HP1α)—in silencing. Immunofluorescence studies indicate that Orc2 HP1α localize on mouse cells. Depletion by shRNA leads to loss both localization Xi. Furthermore, genes disrupted Orc2- HP1α-depleted Finally, show, using ChIP assay, promoter regions Xi-silenced interdependent. These findings reveal silencing, show how impact provide basis for future

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