Loss 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 sufficient to restore xist rna localization during b cell activation. together,our results indicate that xist rna localization is critical for maintaining xci in female lymphocytes,and that chromatin changes on the xi during b cell development and the dynamic nature of yy1-dependent xci maintenance in mature b cells predisposes x-linked immunity genes to reactivation. © 2017 syrett et al.