作者: K. M. Chan , H. Zhang , L. Malureanu , J. van Deursen , Z. Zhang
关键词: Small hairpin RNA 、 Gene silencing 、 ORC2 、 Genetics 、 Heterochromatin protein 1 、 Origin recognition complex 、 X-inactivation 、 X chromosome 、 Biology 、 RNA 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