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Capture Hi-C in TX1072 XXΔXic and XO mESCs in the naive pluripotent state and during differentiation

ABSTRACT: Developmental genes are controlled by complex cis-regulatory landscapes that integrate multiple signals to ensure the correct spatio-temporal expression pattern. To investigate the underlying regulatory principles, we use the Xist locus as a model, which encodes the master regulator of X-chromosome inactivation. Xist is upregulated at the primed pluripotent state in a female-specific manner, thus integrating developmental cues and X-dosage information. It remains poorly understood how these signals are decoded by the ~800kb genomic region that controls Xist. While a series of repressive cis-regulatory elements have been identified, the distal enhancers that activate Xist transcription remain largely unknown. Here we use capture Hi-C to profile chromatin contacts within the X inactivation center at the onset of random X-chromosome inactivation using an endogenous cell model of the inactive (TX 1072 XXΔXic) and active (TX 1072 XO) X chromosome.

ORGANISM(S): Mus musculus

PROVIDER: GSE167351 | GEO | 2021/03/04

REPOSITORIES: GEO

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RNA-seq in TX1072 XO mESCs during differentiation

Project description:As the master regulator of X-chromosome inactivation (XCI), the Xist RNA is expressed nearly ubiquitously in female mice. Xist is only absent in the germ line and at the pluripotent state. Xist is generally assumed to be expressed “by default” in females, while being actively repressed in the few tissues where it is silent. Whether activating mechanisms also contribute remained largely unknown. Through a pooled CRISPR screen we identify the GATA family of transcription factors as potent direct activators of Xist. We describe a GATA-responsive regulatory element (RE79), located ~100 kb upstream of the Xist promoter. In cell lines derived from the two extraembryonic lineages, XEN and TS cells, where imprinted Xist expression is maintained, RE79 is bound by different sets of GATA factors expressed in those tissues. Here we use RNA-seq on differentiating XO mouse embryonic stem cells as a reference for gene expression during early differentiation.

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