A Transcription Cycle

Abstract

Regulation of gene expression by the nuclear estrogen receptor is stimulated in response to binding ligand and involves the recruitment and assembly of multiprotein complexes. Métivier et al. used the pS2 gene promoter as a model for a gene stimulated by human estrogen receptor α. Using chromatin immunoprecipitation (CHIP) analysis, they found more than 30 proteins that bind to the promoter in the presence of estrogen; however, many of these interactions were mutually exclusive. The complexes formed could be grouped into six different classes. In order to analyze the order of protein complex assembly, the basal unstimulated promoter was cleared of all bound proteins, and local histones were deacetylated by synchronization of the cells with α-amantin. Kinetic CHIP analysis was performed to determine the order of complex assembly, and histone modifications were also monitored. Their analysis permitted the identification of three types of cycles of ordered complex assembly and disassembly and chromatin modification, which they present in a model for the formation of one transcriptionally silent cycle followed by two different transcriptionally active types of cycles. R. Métivier, G. Penot, M. R. Hübner, G. Reid, H. Brand, M. Koš, F. Gannon, Estrogen receptor-α directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell 115 , 751-763 (2003). [Online Journal]