Onecut transcription factors are required to maintain Islet1 (Isl1) expression in developing spinal motor neurons (MNs), and this process is critical for proper MN differentiation. However, the mechanisms whereby OC stimulate Isl1 expression remain unknown. CREB-binding protein (CBP) and p300 paralogs are transcriptional coactivators that interact with OC proteins in hepatic cells. In the embryonic spinal cord, CBP and p300 play key roles in neurogenesis and MN differentiation. Here, using chromatin immunoprecipitation and in ovo electroporation in chicken spinal cord, we provide evidence that CBP and p300 contribute to the regulation of Isl1 expression by the OC factors in embryonic spinal MNs. CBP and p300 are detected on the CREST2 enhancer of Isl1 where OC factors are also bound. Inhibition of CBP and p300 activity inhibits activation of the CREST2 enhancer and prevents the stimulation of Isl1 expression by the OC factors. These observations suggest that CBP and p300 coactivators cooperate with OC factors to maintain Isl1 expression in postmitotic MNs.

中文翻译：

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CBP和p300共激活因子通过Onecut转录因子在胚胎脊髓运动神经元中维持Isl1表达。

Onecut转录因子是维持发育中的脊髓运动神经元（MNs）中Islet1（Isl1）表达所必需的，而这一过程对于适当的MN分化至关重要。但是，OC刺激Isl1表达的机制仍然未知。CREB结合蛋白（CBP）和p300旁系同源物是与肝细胞中OC蛋白相互作用的转录共激活因子。在胚胎脊髓中，CBP和p300在神经发生和MN分化中起关键作用。在这里，使用染色质免疫沉淀和卵电穿孔在鸡脊髓中，我们提供了证据，CBP和p300有助于OC因子调节胚胎脊髓MN中的Isl1表达。在Isl1的CREST2增强子上也检测到了CBP和p300，其中还结合了OC因素。CBP和p300活性的抑制抑制了CREST2增强子的激活，并阻止了OC因子刺激Isl1表达。这些观察结果表明，CBP和p300共激活因子与OC因子共同维持有丝分裂后MN中的Isl1表达。