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  • Genetic Intersection of Tsix and Hedgehog Signaling during the Initiation of X-Chromosome Inactivation.

Genetic Intersection of Tsix and Hedgehog Signaling during the Initiation of X-Chromosome Inactivation.

Developmental cell (2017-11-07)
Brian C Del Rosario, Amanda M Del Rosario, Anthony Anselmo, Peggy I Wang, Ruslan I Sadreyev, Jeannie T Lee
ABSTRACT

X-chromosome inactivation (XCI) silences one X chromosome in the female mammal and is essential to peri-implantation development. XCI is thought to be cell autonomous, with all factors required being produced within each cell. Nevertheless, external cues may exist. Here, we search for such developmental signals by combining bioinformatic, biochemical, and genetic approaches. Using ex vivo and in vivo models, we identify the Hedgehog (HH) paracrine system as a candidate signaling cascade. HH signaling keeps XCI in check in pluripotent cells and is transduced by GLI transcription factors to binding sites in Tsix, the antisense repressor of XCI. GLI potentiates Tsix expression and impedes XCI. In vivo, mutating Indian Hedgehog results in a sex ratio bias against females, and the female lethality is rescued by a second-site mutation in Tsix. These data demonstrate a genetic and functional intersection between HH and XCI and support a role for intercellular signaling during XCI.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
Anti-OCT-4 [POU5F1] Antibody, clone 7F9.2, Alexa Fluor 488 conjugate, clone 7F9.2, from mouse, ALEXA FLUOR 488