Chromatin modification of Notch targets in olfactory receptor neuron diversification

• Published in: Nature neuroscience Vol. 15; no. 2; pp. 224 - 233
• Main Authors: Endo, Keita, Karim, M Rezaul, Taniguchi, Hiroaki, Krejci, Alena, Kinameri, Emi, Siebert, Matthias, Ito, Kei, Bray, Sarah J, Moore, Adrian W
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2012; Nature Publishing Group
• Subjects: 631/136/142; 631/378/2624; 631/378/368; 631/80/86; Animal Genetics and Genomics; Animals; Animals, Genetically Modified; Axons - physiology; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Cell differentiation; Cell Differentiation - genetics; Cell Division - genetics; Cell Line; Chromatin; Chromatin - physiology; Chromatin Immunoprecipitation; Daughters; Diversification; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drosophila; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Epigenetics; Gene Expression Regulation, Developmental - genetics; Gene Expression Regulation, Developmental - physiology; Green Fluorescent Proteins - genetics; Insects; Larva; Localization; Mutation - genetics; Neurobiology; Neurogenesis; Neurosciences; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Olfactory Pathways - cytology; Olfactory Pathways - growth & development; Olfactory Receptor Neurons - cytology; Olfactory Receptor Neurons - physiology; Olfactory receptors; Physiological aspects; Proteins; Receptors, Notch - genetics; Receptors, Notch - metabolism; Receptors, Odorant - classification; Receptors, Odorant - genetics; Receptors, Odorant - metabolism; RNA, Messenger - metabolism; Signal transduction; Signal Transduction - physiology; Statistics, Nonparametric; Transcription Factors - genetics; Transcription Factors - metabolism; Transfection; Czech Republic; Japan
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.2998

This study shows a new molecular mechanism governing olfactory receptor neuron (ORN) subtype diversification from a shared precursor cell. Selection of ORNs in Drosophila is mediated by Notch signaling. Chromatin modifications directed to specific genes targeted by Notch modify the responses to this signal and diversify ORN identity and circuitry. Neuronal-class diversification is central during neurogenesis. This requirement is exemplified in the olfactory system, which utilizes a large array of olfactory receptor neuron (ORN) classes. We discovered an epigenetic mechanism in which neuron diversity is maximized via locus-specific chromatin modifications that generate context-dependent responses from a single, generally used intracellular signal. Each ORN in Drosophila acquires one of three basic identities defined by the compound outcome of three iterated Notch signaling events during neurogenesis. Hamlet, the Drosophila Evi1 and Prdm16 proto-oncogene homolog, modifies cellular responses to these iteratively used Notch signals in a context-dependent manner, and controls odorant receptor gene choice and ORN axon targeting specificity. In nascent ORNs, Hamlet erases the Notch state inherited from the parental cell, enabling a modified response in a subsequent round of Notch signaling. Hamlet directs locus-specific modifications of histone methylation and histone density and controls accessibility of the DNA-binding protein Suppressor of Hairless at the Notch target promoter.