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.

Abstract:

: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.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Syrett CM,Sindhava V,Hodawadekar S,Myles A,Liang G,Zhang Y,Nandi S,Cancro M,Atchison M,Anguera MC

doi

10.1371/journal.pgen.1007050

subject

Has Abstract

pub_date

2017-10-09 00:00:00

pages

e1007050

issue

10

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-17-00735

journal_volume

13

pub_type

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