Haematopoietic stem and progenitor cells (HSPCs) have been the focus of developmental and regenerative studies, yet our understanding of the signalling events regulating their specification remains incomplete. We demonstrate that supt16h, a component of the Facilitates chromatin transcription (FACT) complex, is required for HSPC formation. Zebrafish supt16h mutants express reduced levels of Notch-signalling components, genes essential for HSPC development, due to abrogated transcription. Whereas global chromatin accessibility in supt16h mutants is not substantially altered, we observe a specific increase in p53 accessibility, causing an accumulation of p53. We further demonstrate that p53 influences expression of the Polycomb-group protein PHC1, which functions as a transcriptional repressor of Notch genes. Suppression of phc1 or its upstream regulator, p53, rescues the loss of both Notch and HSPC phenotypes in supt16h mutants. Our results highlight a relationship between supt16h, p53 and phc1 to specify HSPCs via modulation of Notch signalling.

造血干细胞和祖细胞 (HSPC) 一直是发育和再生研究的重点，但我们对调节其规格的信号事件的理解仍然不完整。我们证明supt16h是促进染色质转录 (FACT) 复合物的一个组成部分，是 HSPC 形成所必需的。斑马鱼supt16h突变体表达的 Notch 信号成分水平降低，这些成分是 HSPC 发育所必需的基因，由于转录被取消。虽然supt16h突变体中的全局染色质可及性没有显着改变，但我们观察到p53的特定增加可及性，导致 p53 的积累。我们进一步证明 p53 影响 Polycomb 组蛋白 PHC1 的表达，该蛋白充当 Notch 基因的转录抑制因子。抑制phc1或其上游调节因子 p53可挽救supt16h突变体中 Notch 和 HSPC 表型的丧失。我们的结果强调了supt16h、p53和phc1之间的关系，以通过调制 Notch 信号来指定 HSPC。