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.
PLoS Genet
; 13(10): e1007050, 2017 Oct.
Article
in En
| MEDLINE
| ID: mdl-28991910
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.
Full text:
1
Database:
MEDLINE
Main subject:
Lymphocyte Activation
/
Gene Silencing
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YY1 Transcription Factor
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X Chromosome Inactivation
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Precursor Cells, B-Lymphoid
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RNA, Long Noncoding
Language:
En
Journal:
PLoS Genet
Year:
2017
Type:
Article
Affiliation country:
United States