Xist expression impacts chromatin structure and YY1 mediated transcription of X-linked genes in hematopoietic progenitor cells

Yang, T.; Ou, J.; Yildirim, E.

doi:10.1101/2022.02.16.480654

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bioRxiv · 10.1101/2022.02.16.480654

Xist expression impacts chromatin structure and YY1 mediated transcription of X-linked genes in hematopoietic progenitor cells

Yang, T.·Ou, J.·Yildirim, E.

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Abstract

X chromosome inactivation (XCI) is a dosage compensation phenomenon that occurs in females. Initiation of XCI depends on Xist RNA, which triggers silencing of one of the two X chromosomes, except for genes that escape XCI. This inactive state is propagated during cell divisions with continuous Xist expression. How Xist impacts XCI maintenance remains an open question. Here, we delete Xist in hematopoietic cells of mice and report increased fraction of cycling hematopoietic progenitors and differentiation defects during hematopoiesis. Xist loss results in upregulation of a subset of X-linked genes, several of which escape XCI and have functions in hematopoiesis and immunity. We find that the underlying mechanism of transcriptional upregulation involves reduced H3K27me3 occupancy and increased chromatin accessibility which accommodate binding of YY1 transcription factor (TF). We propose that XCI maintenance defects in Xist deficient mice rely on the landscape of open chromatin sites, TF availability, and cell cycle stress in specific cellular context during hematopoiesis.

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Yang, T., Ou, J., Yildirim, E.. 2022-02-16. Xist expression impacts chromatin structure and YY1 mediated transcription of X-linked genes in hematopoietic progenitor cells. https://doi.org/10.1101/2022.02.16.480654

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