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Working model: FACT maintains ES cell pluripotency through regulation of pluripotency factor expression. FACT binds to gene-distal cis-regulatory elements (promoters and enhancers) and regulates both ncRNA transcription and nucleosome occupancy at these regulatory locations to permit appropriate expression of mRNAs. When FACT is depleted through IAA treatment, nucleosome occupancy at cis-regulatory elements is increased and mRNA expression is altered. These changes result in a loss of pluripotency and initiation of irregular differentiation across all 3 germ layers. OSN = OCT4, SOX2, and/or NANOG. Created with Biorender.com

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