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

Overview

Journal PLoS Genet

Specialty Genetics

Date 2017 Oct 10

PMID 28991910

Citations 55

Authors

Camille M Syrett

Vishal Sindhava

Suchita Hodawadekar

Arpita Myles

Guanxiang Liang

Yue Zhang

Satabdi Nandi

Michael Cancro

Michael Atchison

Montserrat C Anguera

Affiliations

Soon will be listed here.

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.

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