RECEPTOR BINDING FACTOR FOR THE AH-RECEPTOR

为了更好地了解参与细胞机制， 我们会研究环境污染物二恶荚的各种影响， 染色质中Ah受体的特异性受体结合因子（RBFs）。 不同动物物种和组织对 二恶英的部分原因可能是某些物质的存在或不存在。 核基质中的AhRBFs。 此外， 二恶英可以解释为Ah受体与某些 子宫雌激素RBFs 这些研究也将针对穷人 某些化合物的生物学效应与其 对Ah受体或受体复合物的体外结合亲和力 与二恶英反应元件结合。 我们必须先净化肝脏 和子宫AhRBFs。 其氨基酸序列的测定将 允许与其他DNA结合蛋白进行比较，特别是RBFs， 类固醇激素 制备这些AhRBFs的抗体将使我们能够 以确定这些染色体蛋白质是否与细胞核 基质中的物种和组织特异性的方式。 还建议进行研究 研究AhRBFs在基因转录中的作用， 瞬时和稳定转染实验。 我们将决定是否和 AhRBFs与已知的二恶英诱导基因相关，如 CYP1A1或CYP1A2，并确定与之相关的共有DNA序列， 这些AhRBFs绑定。

In order to better understand the cellular mechanisms involved in the diverse effects of the environmental contaminant, dioxin, we will study specific receptor binding factors (RBFs) for the Ah receptor in chromatin. The differential sensitivity of various animal species and tissues to dioxin may be explained, in part, by the absence or presence of certain AhRBFs in the nuclear matrix. In addition, the antiestrogenic actions of dioxin may be explained by interaction of the Ah receptor with certain uterine estrogen RBFs. These studies will also address the poor correlation between biological effectiveness of some compounds and their in vitro binding affinity for the Ah receptor or for receptor complex binding to dioxin response elements. We must first purify select liver and uterine AhRBFs. Determination of their amino acid sequences will allow for comparisons with other DNA binding proteins, especially RBFs for steroid hormones. Preparation of antibodies to these AhRBFs will allow us to determine if these chromosomal proteins are associated with the nuclear matrix in a species and tissue specific manner. Studies are also proposed to investigate the role of AhRBFs in gene transcription utilizing both transient and stable transfection experiments. We will determine if and where AhRBFs are associated with known dioxin-inducible genes, such as CYP1A1 or CYP1A2 and also determine the consensus DNA sequence to which these AhRBFs bind.