title: The Drosophila enhancer of split gene complex: architecture and coordinate regulation by notch, cohesin, and polycomb group proteins.
abstract: The cohesin protein complex functionally interacts with Polycomb group (PcG) silencing proteins to control expression of several key developmental genes, such as the Drosophila Enhancer of split gene complex [E(spl)-C]. The E(spl)-C contains 12 genes that inhibit neural development. In a cell line derived from the central nervous system, cohesin and the PRC1 PcG protein complex bind and repress E (spl)-C transcription, but the repression mechanisms are unknown. The genes in the E(spl)-C are directly activated by the Notch receptor. Here we show that depletion of cohesin or PRC1 increases binding of the Notch intracellular fragment to genes in the E(spl)-C, correlating with increased transcription. The increased transcription likely reflects both direct effects of cohesin and PRC1 on RNA polymerase activity at the E(spl)-C, and increased expression of Notch ligands. By chromosome conformation capture we find that the E(spl)-C is organized into a self-interactive architectural domain that is co-extensive with the region that binds cohesin and PcG complexes. The self-interactive architecture is formed independently of cohesin or PcG proteins. We posit that the E(spl)-C architecture dictates where cohesin and PcG complexes bind and act when they are recruited by as yet unidentified factors, thereby controlling the E(spl)-C as a coordinated domain.
authors: Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, Missouri 63104.
authors: Cheri A
authors: CA
authors: Schaaf
authors: Ziva
authors: Z
authors: Misulovin
authors: Maria
authors: M
authors: Gause
authors: Amanda
authors: A
authors: Koenig
authors: Dale
authors: D
authors: Dorsett
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D059006:Chromosomes, Insect / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D063146:Polycomb-Group Proteins / Q000378:metabolism*; D011485:Protein Binding; D051880:Receptors, Notch / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015533:Transcriptional Activation; D000097722:Cohesins
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D063146:Polycomb-Group Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; C121960:E(spl)m7-HLH protein, Drosophila; C497759:N protein, Drosophila; C506513:cohesin protein complex, Drosophila; D000097722:Cohesins
keywords: Chromator; Nipped-B; Putzig; RNA polymerase; Suppressor of Hairless
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