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The bipartite TAD organization of the X-inactivation centre ensures opposing developmental regulation of Tsix and Xist

ABSTRACT: The mouse X-inactivation center (Xic) locus represents a powerful model for understanding the links between genome architecture and gene regulation, with the non-coding genes Xist and Tsix showing opposite developmental expression patterns while being organized as an overlapping sense/antisense unit. The Xic is organized into two topologically associating domains (TADs) but the role of this architecture in orchestrating cis-regulatory information remains elusive. To explore this, we generated genomic inversions within the Xic that swap the Xist/Tsix transcriptional unit and place their promoters in each other’s TAD. We found that this led to a switch in their expression dynamics: Xist became precociously and ectopically up-regulated, both in male and female pluripotent cells, while Tsix expression aberrantly persisted during differentiation. The topological partitioning of the Xic is thus critical to ensure proper developmental timing of X-inactivation. Our study illustrates how genomic architecture can hardwire the potential for mammalian developmental regulation by cis-regulatory landscapes.

ORGANISM(S): Mus musculus

PROVIDER: GSE111205 | GEO | 2019/05/27

REPOSITORIES: GEO

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

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The bipartite TAD organization of the X-inactivation centre ensures opposing developmental regulation of Tsix and Xist

Project description:The bipartite TAD organization of the X-inactivation centre ensures opposing developmental regulation of Tsix and Xist

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ChIP-sequencing (ChIP-seq) experiments on female ESCs expressing V5-tagged REX1 and control wild-type Embryonic stem cells (ESCs)

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STARR-seq in 1.8 XX and XO mESCs during differentiation

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RNA-seq of mouse ES cells depleted of MOF, MSL1, MSL2 or KANSL3

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