On January 10, 2012, Prof. Xu Guotong, Professor of Tongji University School of Medicine published a research paper an international academic thesis in Journal of Cell Science. The thesis named,“Binding of the ERa and ARNT1 AF2 domains to exon 21 of the SRC1 isoform SRC1e is essential for estrogen and dioxin-related transcription "。The paper found that the binding site of the estrogen receptor to active domain 2 on ARNT1 is at the C-terminus of SRC1, demonstrating that this binding can up-regulate estrogen and dioxin-induced related reactivity in mammalian cells. SRC 1 is a transcriptional coactivator of many transcription factors involved in nuclear receptors. ARNT1 is an essential partner for the transcription of aromatic hydrocarbon receptors and hypoxia-inducible factor-1a (HIF-1a) and is also a coactivator of the estrogen receptor. In the present study, researcher Dr. Endler and colleagues found that estrogen-activated AF2 on transcriptional activation interacts with the LxxLL region on the NID on SRC1. Estrogen and LxxLL domains that are not affected by AF2 can act on exon 21 of SRC 1; in addition, exon 16 of ARNT1 can bind exon 21 of SRC 1. Interestingly, the combination of exon 21 and AF2 of SRC 1 can be an estrogen-induced important transcriptional enhancer. The binding of active domain 2 on ARNT1 to exon 21 of SRC 1 enhances the transcriptional response to dioxins but this upregulation reaction is essentially dependent on the two D-cassettes. This D-cassettes is exactly on the 16th exon of ARNT1.

The research project has been funded by the Ministry of Science and Technology, the National Natural Science Foundation of China, the Shanghai Municipal Science and Technology Commission and the Chinese Academy of Sciences.