OCT4 and SOX2 confer pluripotency by recruiting coactivators to activate stem cell-specific gene expression programs. However, the composition of coactivator complexes and their roles in maintaining stem cell fidelity remain unclear. Here we report the identification of ATP-binding cassette subfamily F member 1 (ABCF1) as a critical coactivator for OCT4/SOX2. ABCF1 is required for pluripotency gene expression and stem cell self-renewal. ABCF1 binds co-dependent coactivators XPC and DKC1 via its intrinsically disordered region and stimulates transcription by linking SOX2 to the transcription machinery. Furthermore, in response to pathogen infection and DNA damage, ABCF1 binds intracellular DNAs accumulated in cells, concomitant with loss of SOX2 interaction and pluripotency gene transcription. This results in spontaneous differentiation of compromised stem cells and elimination from the self-renewing population. Thus, ABCF1 directly couples pluripotency gene transcription with sensing aberrant DNAs and acts as a checkpoint for self-renewal to safeguard stem cell fidelity and genome integrity.

中文翻译：

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ATP结合盒蛋白ABCF1将基因转录与胚胎干细胞中基因组完整性的维持相结合

OCT4和SOX2通过募集共激活剂激活干细胞特异性基因表达程序来赋予多能性。然而，尚不清楚共激活复合物的组成及其在维持干细胞保真度中的作用。在这里，我们报告的ATP结合盒亚家族F成员1（ABCF1）作为OCT4 / SOX2的关键共激活因子的鉴定。多能性基因表达和干细胞自我更新需要ABCF1。ABCF1通过其固有的无序区结合共依赖性共激活因子XPC和DKC1，并通过将SOX2连接到转录机制来刺激转录。此外，响应病原体感染和DNA损伤，ABCF1结合细胞中积累的细胞内DNA，并伴随SOX2相互作用和多能性基因转录的丧失。这导致受损干细胞的自发分化并从自我更新的种群中消除。因此，ABCF1将多能性基因转录与传感异常DNA直接耦合，并充当自我更新的检查点，以维护干细胞保真度和基因组完整性。