Center for Biomedical Research, Universidad Andres Bello, Santiago, Chile.
J Cell Physiol. 2013 Apr;228(4):860-70. doi: 10.1002/jcp.24236.
Transient Receptor Potential Vanilloid type 1 channel (TRPV1) is an important endogenous transducer of noxious heat and chemical stimuli and is required during development of inflammatory hypersensitivity. The transcription factor Runx1 is known to play a relevant role in sensory neuron differentiation as it controls the expression of several sensory nociceptive receptors, including TRPV1. Here, we show that Runx1 up-regulates TRPV1 transcription activity by interacting directly with the proximal TRPV1 gene promoter sequence. Importantly, C/EBPβ a well-established heterodimer partner of Runx1 also binds to the TRPV1 promoter and cooperates with Runx1 to further stimulate TRPV1 transcription. Our results support a mechanism where Runx1-C/EBPβ-containing transcription regulatory complexes are recruited to the TRPV1 gene promoter to modulate TRPV1 expression in dorsal root ganglia neurons.
瞬时受体电位香草酸亚型 1 通道（TRPV1）是伤害性热和化学刺激的重要内源性传感器，在炎症性超敏反应的发展过程中是必需的。转录因子 Runx1 已知在感觉神经元分化中发挥相关作用，因为它控制包括 TRPV1 在内的几种感觉伤害性受体的表达。在这里，我们表明 Runx1 通过与 TRPV1 基因启动子序列的近端直接相互作用而上调 TRPV1 转录活性。重要的是，C/EBPβ是 Runx1 的成熟异二聚体伴侣，也与 TRPV1 启动子结合，并与 Runx1 合作进一步刺激 TRPV1 转录。我们的结果支持这样一种机制，即包含 Runx1-C/EBPβ的转录调节复合物被募集到 TRPV1 基因启动子，以调节背根神经节神经元中的 TRPV1 表达。
