Genes Ancestral To The Thyroid/steroid Receptor Family

甲状腺/类固醇受体家族的祖先基因

• 批准号: 6677474
• 负责人: JOSEPH EDWARD RALL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6677474
• 关键词: Caenorhabditis elegans; Cnidaria; DNA binding protein; biochemical evolution; chemical structure function; complementary DNA; crystallins; developmental genetics; gene mutation; genetic mapping; genetic regulation; hormone receptor; invertebrate embryology; invertebrate hormone; lens; methionine; polymerase chain reaction; protein structure function; skin; steroid hormone receptor; thyroid hormones; tissue /cell culture

We are studying nuclear hormone receptors in invertebrates. In continuation of our work on CHR3, a nuclear hormone receptor that is important for C. elegans development (1,2), we searched for interacting cofactors. We performed RNA interference experiments directed to inhibit genes that we identified by homology to known cofactors and searched for phenotypic changes similar to CHR3 loss of function. We found that inhibition of C.elegans SKIP (CeSKIP)leads to phenotypic changes partially overlapping with CHR3. SKIP is a cofactor identified in multiple regulatory pathways such as Notch, TGFbeta and vitamin D receptor, and is conserved between plants, yeast and animals. CeSKIP is essential for C. Elegans viability and development. Our results also showed that despite phosphorylation of the RNA Pol II C-terminal domain (CTD), CeSKIP RNAi embryos arrest with a phenotype similar to the loss of RNA Pol II activity and fail to express multiple embryonic GFP reporter genes, as well as an endogenous gene (dpy-7). We also found that C. elegans SKIP is co-transcribed with bir-1, an inhibitor of apoptosis that is homologeous to mammalian Surviving (3). Because genes organized in operons are often linked functionally, we have been studying if bir-1 has beyond its known function in cell division, also a role in regulation of transcription by RNA polymerase II. We found that bir-1 has a developmental regulatory role and its loss of function has partially overlapping phenotype with CeSKIP and CHR3. We also found, that several transgenes as well as endogenous dpy-7 are inhibited as consequence of bir-1 loss of functiion. bir-1 acts as co-activator in a heterologus transfection system including thyroid hormone receptor beta 1. We are currently trying to find the mechanism by which Bir-1 influences transcription by RNA polymerase II.

我们正在研究无脊椎动物的核激素受体。CHR3是一种核激素受体，对秀丽隐杆线虫的发育起重要作用（1,2），为了继续我们对CHR3的研究，我们寻找了相互作用的辅因子。