Abstract：
Forkhead box P2 (FOXP2) regulates expression of various genes and is associated with language, speech and neural development as well as cancer. Since there may be a putative link between sex and language and because transcription factors rarely function in isolation, this study aims to investigate whether FOXP2 directly associates with oestrogen receptor α (ER1), a nuclear receptor responsible for sexual differentiation that is also associated with cancer. Isothermal titration calorimetry and fluorescence anisotropy were used to investigate the interaction between the DNA-binding forkhead domain (FHD) of FOXP2, the N-terminal region (NT) of FOXP2, and the ligand-binding domain (LBD) of ER1. ER1 LBD does not interact with FOXP2 NT but associates with apo-FOXP2 FHD in an enthalpically favourable manner. The affinity of this interaction is inversely correlated to the salt concentration. Additionally, FOXP2 FHD that is bound to ER1 LBD, has reduced ability to interact with its cognate DNA. This research identifies a novel interaction between ER1 LBD and FOXP2 FHD and shows that the interaction is regulated by salt. Moreover, FOXP2 FHD cannot bind to both ER1 LBD and DNA simultaneously, suggesting that this interaction could be involved in regulating the transcriptional pathway of FOXP2 should the interaction be found in vivo. This study could serve as a foundation for uncovering the basis of sexual dimorphism in speech and language development and related disorders and potentially offers an alternate for targeted cancer therapies.
摘要：
叉头盒P2（FOXP2）调节各种基因的表达，并与语言，语言和神经发育以及癌症。由于性别和语言之间可能存在推定的联系，并且转录因子很少孤立地发挥作用，这项研究旨在探讨FOXP2是否与雌激素受体α（ER1）直接相关，负责性分化的核受体，也与癌症有关。等温滴定量热法和荧光各向异性用于研究FOXP2的DNA结合叉头域（FHD），FOXP2的N端区域（NT）和ER1的配体结合域（LBD）之间的相互作用。ER1LBD不与FOXP2NT相互作用，但以有利的方式与apo-FOXP2FHD结合。这种相互作用的亲和力与盐浓度成反比。此外,FOXP2FHD与ER1LBD绑定，降低了与其同源DNA相互作用的能力。这项研究确定了ER1LBD和FOXP2FHD之间的新相互作用，并表明该相互作用受盐调节。此外，FOXP2FHD不能同时与ER1LBD和DNA结合，这表明，如果在体内发现这种相互作用，这种相互作用可能参与调节FOXP2的转录途径。这项研究可以作为揭示言语和语言发育以及相关疾病中性二态性基础的基础，并可能为靶向癌症治疗提供替代方案。
