Psi, the sole FUSE Binding Protein (FUBP) family single stranded DNA/RNA binding protein in Drosophila, is essential for proper cell and tissue growth, however its mechanism of function remains unclear. Here we use Targeted DamID combined with RNA-sequencing to generate the first genome-wide binding and expression profiles for Psi. Surprisingly, we demonstrate Psi drives growth in the Drosophila wing through transcriptional repression of key developmental pathways (e.g. Wnt, Notch and TGFβ). Thus, Psi patterns tissue growth by directly repressing transcription of developmental growth suppressors. Analysis of direct Psi targets identified novel growth inhibitors, including Tolkin (Zinc metallopeptidase implicated in TGFβ signalling), Ephexin (Rho-GEF) and emp (CD36 scavenger receptor-related protein). Their depletion not only suppressed impaired growth associated with Psi knockdown, but alone was sufficient to drive wing overgrowth. Thus, Psi drives wing growth twofold, through direct activation of Myc and through transcriptional repression of growth inhibitors comprising core developmental pathways.

中文翻译：

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Psi通过抑制关键发育网络的转录来促进果蝇翅膀的生长

Psi是果蝇中唯一的FUSE结合蛋白（FUBP）家族单链DNA / RNA结合蛋白，对于细胞和组织的正常生长至关重要，但是其功能机制仍不清楚。在这里，我们将Targeted DamID与RNA测序结合使用，以生成Psi的第一个全基因组范围的结合和表达谱。出人意料的是，我们证明了Psi通过关键发育途径（例如Wnt，Notch和TGFβ）的转录抑制来驱动果蝇翼的生长。因此，Psi通过直接抑制发育生长抑制剂的转录来图案化组织生长。对直接Psi靶标的分析鉴定出了新的生长抑制剂，包括Tolkin（与TGFβ信号传导有关的锌金属肽酶），麻黄素（Rho-GEF）和emp（CD36清道夫受体相关蛋白）。它们的耗竭不仅抑制了与Psi抑制相关的生长减慢，而且仅此一项就足以促使机翼过度生长。因此，Psi通过直接激活Myc并通过转录抑制包括核心发育途径的生长抑制剂来驱动翅膀的生长。