biostudies-literatureSyrett CMNational Institute of Allergy and Infectious DiseasesNICHD NIH HHSLupus Foundation of AmericaNIAID NIH HHSNational Institute of General Medical SciencesNational Institute of Child Health and Human DevelopmentNIGMS NIH HHSe1007050https://www.ebi.ac.uk/biostudies/studies/S-EPMC5648283biostudies-literatureUnknown13(10)X-chromosome inactivation (XCI) in female lymphocytes is uniquely regulated, as the inactive X (Xi) chromosome lacks localized Xist RNA and heterochromatin modifications. Epigenetic profiling reveals that Xist RNA is lost from the Xi at the pro-B cell stage and that additional heterochromatic modifications are gradually lost during B cell development. Activation of mature B cells restores Xist RNA and heterochromatin to the Xi in a dynamic two-step process that differs in timing and pattern, depending on the method of B cell stimulation. Finally, we find that DNA binding domain of YY1 is necessary for XCI in activated B cells, as ex-vivo YY1 deletion results in loss of Xi heterochromatin marks and up-regulation of X-linked genes. Ectopic expression of the YY1 zinc finger domain is sufficiePLoS geneticsLoss of Xist RNA from the inactive X during B cell development is restored in a dynamic YY1-dependent two-step process in activated B cells.PMC5648283RO1 GM111384RO1 AI079002T32-GM007229T32-HD083185K12 HD085848R01 AI079002R21 AI124084HD085848T32 GM007229T32 HD083185R01 GM111384Sindhava VAnguera MCSyrett CMMyles ALiang GCancro MHodawadekar SZhang YAtchison MNandi SfalseLoss of Xist RNA from the inactive X during B cell development is restored in a dynamic YY1-dependent two-step process in activated B cells.X-chromosome inactivation (XCI) in female lymphocytes is uniquely regulated, as the inactive X (Xi) chromosome lacks localized Xist RNA and heterochromatin modifications. Epigenetic profiling reveals that Xist RNA is lost from the Xi at the pro-B cell stage and that additional heterochromatic modifications are gradually lost during B cell development. Activation of mature B cells restores Xist RNA and heterochromatin to the Xi in a dynamic two-step process that differs in timing and pattern, depending on the method of B cell stimulation. Finally, we find that DNA binding domain of YY1 is necessary for XCI in activated B cells, as ex-vivo YY1 deletion results in loss of Xi heterochromatin marks and up-regulation of X-linked genes. Ectopic expression of the YY1 zinc finger domain is sufficie2017-01-01T00:00:00Z2017 Oct2026-04-08T02:46:31.876Z2026-04-07T21:02:56.487ZS-EPMC56482832899191010.1371/journal.pgen.1007050