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Non-coding CRISPR interference screen to identify regulatory elements of Xist in TX1072 XX SP107 mESCs at the onset of random X inactivation

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 an inducible CRISPRi system in a non-coding CRISPR screen to profile 138 candidate regulatory elements on their effect on Xist upregulation during early differentiation of mouse Embryonic Stem Cells (mESCs).

ORGANISM(S): synthetic construct Mus musculus

PROVIDER: GSE167352 | GEO | 2021/03/04

REPOSITORIES: GEO

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PolyA-tail enriched RNA-seq in differentiating TX1072 XX mESCs

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Project description: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.

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A conserved noncoding locus modulates random monoallelic Xist expression across a TAD boundary

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Non-coding CRISPR interference screen to identify regulatory elements of Xist in TX1072 XX SP107 mESCs at the onset of random X inactivation

Project description:Non-coding CRISPR interference screen to identify regulatory elements of Xist in TX1072 XX SP107 mESCs at the onset of random X inactivation

| PRJNA704374 | ENA

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