FGF4 initiates X-chromosome inactivation via activating YY1 and prompting loss of pluripotency factors

ABSTRACT: X-chromosome inactivation (XCI) balances gene expression between sexes in mammals, and is essential to female development. XCI initiation strictly relies on the upregulation of long noncoding RNA Xist upon differentiation. Despite the co-occurrence and tight correlation between XCI and differentiation, master coordinators to synchronize XCI and differentiation remain ill-defined. Here, we report that FGF4, an autocrine differentiation-prompting stimulus, is essential for Xist upregulation and XCI initiation in mouse embryonic stem cells (ESCs). Either Fgf4 deficiency or FGFR blocking results in failure of Xist upregulation and XCI initiation. Mechanistically, FGF4 initiates XCI in a MEK/ERK-dependent manner, via two parallel but opposing pathways: i) FGF4 phosphorylates and activates YY1,

SUBMITTER: Lizhu Ma 

PROVIDER: S-SCDT-10_1038-S44318-026-00722-2 | biostudies-other |

REPOSITORIES: biostudies-other