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XIST dampens X chromosome activity in a SPEN-dependent manner during early human development [ATAC-seq]

GSE246633 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 6 samples Submitted 2024/04/24 Platform GPL24676
Summary
XIST long non-coding RNA is responsible for X chromosome inactivation (XCI) in placental mammals, yet it accumulates on both X chromosomes in human female pre-implantation embryos without triggering X chromosome silencing. The long non-coding RNA XACT co-accumulates with XIST on active Xs and may antagonize XIST function. Here we used human ES cells in a naïve state of pluripotency to assess the function of XIST and XACT in shaping the X chromosome chromatin and transcriptional landscapes during pre-implantation development. We show that XIST triggers the deposition of polycomb-mediated repressive histone modifications and attenuates transcription of most X-linked genes in a SPEN-dependent manner, while XACT deficiency does not significantly affect XIST activity or X-linked gene expression. Our study demonstrates that XIST is functional prior to XCI, confirms the existence of a transient process of X chromosome dosage compensation, and reveals that X chromosome inactivation and dampening rely on the same set of factors.
Published in
XIST dampens X chromosome activity in a SPEN-dependent manner during early human development
Alfeghaly C, Castel G, Cazottes E et al. · Nature structural & molecular biology 2024 · PMID 38834912 · doi:10.1038/s41594-024-01325-3
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Direct links to NCBI, no account and no request form: the whole study as GSE246633_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1034017 and SRA study SRP469423. Searching any of these in the dataset finder brings you back here.

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