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PI3Kβ and β-Catenin mediate EZH2 removal from promoters controlling human ESC stemness and primitive streak gene expression

ABSTRACT: The mechanism governing the transition of human embryonic stem cells towards differentiated cells is only partially understood. To explore this transition, the activity and expression of the ubiquitous phosphoinositide-3-kinase (PI3K α and β) were modulated. This study reports a pathway that dismantles the repression imposed by the EZH2 polycomb repressor on an essential stemness gene, NODAL, and on transcription factors required at differentiation to trigger primitive streak formation. The primitive streak is the site where gastrulation begins to give rise to the three embryonic cell layers from which all human tissues derive. The pathway involves an essential PI3Kβ-non-catalytic action for control of active-RAC1 levels, c-Jun-Nterminal-kinase activation and nuclear β-CATENIN accumulation. β-CATENIN deposition at promoters triggers the release of EZH2 repressor permitting both stemness maintenance (through control of NODAL) and correct differentiation, by allowing primitive streak master genes expression. PI3Kβ -mediated epigenetic control of EZH2/β-CATENIN might be modulated to direct stem cell differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE202163 | GEO | 2022/07/27

REPOSITORIES: GEO

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PI3Kβ and β-Catenin mediate EZH2 removal from promoters controlling human ESC stemness and primitive streak gene expression

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