SPEN is required for Xist upregulation during initiation of X chromosome inactivation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34853312.
- Also identified by DOI 10.1038/s41467-021-27294-5 and PMC identifier 8636516.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
At initiation of X chromosome inactivation (XCI), Xist is monoallelically upregulated from the future inactive X (Xi) chromosome, overcoming repression by its antisense transcript Tsix. Xist recruits various chromatin remodelers, amongst them SPEN, which are involved in silencing of X-linked genes in cis and establishment of the Xi. Here, we show that SPEN plays an important role in initiation of XCI. Spen null female mouse embryonic stem cells (ESCs) are defective in Xist upregulation upon differentiation. We find that Xist-mediated SPEN recruitment to the Xi chromosome happens very early in XCI, and that SPEN-mediated silencing of the Tsix promoter is required for Xist upregulation. Accordingly, failed Xist upregulation in Spen<sup>-/-</sup> ESCs can be rescued by concomitant removal of Tsix. These findings indicate that SPEN is not only required for the establishment of the Xi, but is also crucial in initiation of the XCI process.
Medical subject headings
- DNA-Binding Proteins
- RNA, Long Noncoding
- RNA-Binding Proteins
- X Chromosome Inactivation