Cell-type-specific chromatin occupancy by the pioneer factor Zelda drives key developmental transitions in Drosophila.
Cell-type-specific chromatin occupancy by the pioneer factor Zelda drives key developmental transitions in Drosophila.
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DOI：
10.1038/s41467-021-27506-y
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发表时间：
2021-12-09
影响因子：
16.6
通讯作者：
Harrison MM
中科院分区：
文献类型：
--
作者：
Larson ED;Komori H;Gibson TJ;Ostgaard CM;Hamm DC;Schnell JM;Lee CY;Harrison MM
在果蝇胚胎发育过程中，关键的先锋因子塞尔达定义了数百个顺式调节区，并在此过程中对合子转录组进行了重新编程。虽然塞尔达在发育后期是必不可少的，但目前还不清楚塞尔达定义顺式调控区域的能力是如何由细胞类型特定的染色质结构塑造的。果蝇脑中神经干细胞(神经母细胞)的不对称分裂为研究这种先驱因子的特定细胞类型的功能提供了一个极好的范例。我们发现Zelda与Notch具有协同作用，以维持神经母细胞处于未分化状态。Zelda错误表达将祖细胞重新编程为神经母细胞，但这种能力受到对祖细胞承诺至关重要的转录抑制因子的限制。与胚胎相比，塞尔达基因在神经母细胞中的占有率发生了重组，这种重组与染色质可及性和辅因子可获得性的差异有关。我们认为，Zelda通过由细胞类型特异性增强子驱动的共享基因调控网络来调节神经母细胞和胚胎中的基本转变。先锋转录因子Zelda是果蝇早期胚胎生殖细胞重新编程为全能细胞所必需的。在这里，作者研究了Zelda在幼虫大脑发育后期的功能，以表明Zelda促进了未分化干细胞的命运。他们进一步确定了限制这一先驱因素重新编程能力的因素。
During Drosophila embryogenesis, the essential pioneer factor Zelda defines hundreds of cis-regulatory regions and in doing so reprograms the zygotic transcriptome. While Zelda is essential later in development, it is unclear how the ability of Zelda to define cis-regulatory regions is shaped by cell-type-specific chromatin architecture. Asymmetric division of neural stem cells (neuroblasts) in the fly brain provide an excellent paradigm for investigating the cell-type-specific functions of this pioneer factor. We show that Zelda synergistically functions with Notch to maintain neuroblasts in an undifferentiated state. Zelda misexpression reprograms progenitor cells to neuroblasts, but this capacity is limited by transcriptional repressors critical for progenitor commitment. Zelda genomic occupancy in neuroblasts is reorganized as compared to the embryo, and this reorganization is correlated with differences in chromatin accessibility and cofactor availability. We propose that Zelda regulates essential transitions in the neuroblasts and embryo through a shared gene-regulatory network driven by cell-type-specific enhancers. The pioneer transcription factor Zelda is essential for the reprogramming of germ cells to totipotent cells of the early Drosophila embryo. Here the authors examine the function of Zelda later in development in the larval brain to show that Zelda promotes the undifferentiated stem-cell fate. They further identify factors that limit the reprogramming capacity of this pioneer factor.
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