title: Robust specification of sensory neurons by dual functions of charlatan, a Drosophila NRSF/REST-like repressor of extramacrochaetae and hairy.
abstract: Sensory bristle formation in Drosophila is a well-characterized system for studying sensory organ development at the molecular level. The master proneural genes of the achaete-scute (ac-sc) complex, which encode basic-helix-loop-helix (bHLH) transcription factors, are necessary and sufficient for sensory bristle formation. charlatan (chn) was originally identified as a transcriptional activator of ac-sc gene expression through interaction with its enhancer, an activity that promotes sensory bristle development. In contrast, Chn was also identified as a functional homologue of mammalian neuron-restrictive silencing factor or RE1 silencing transcription factor (NRSF/REST), an important transcriptional repressor during vertebrate neurogenesis and stem cell development that acts through epigenetic gene silencing. Here, we report that Chn acts as a repressor of extramacrochaetae (emc) and hairy, molecules that inhibit ac-sc expression. This double-negative mechanism, together with direct activation via the achaete enhancer, increases expression of achaete and ensures robust development of sensory neurons. A mutation in the C-terminal repressor motif of Chn, which causes Chn to lose its repression activity, converted Chn to an activator of emc and hairy, suggesting that Chn is a dual functional regulator of transcription. Because chn-like sequences are found among arthropods, regulation of neuronal development by Chn-like molecules may be widely conserved.
authors.affiliation: Animal Model of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.
authors.forename: Yasutoyo
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Lim
authors.forename: Nao
authors.initials: N
authors.lastname: Niwa
authors.forename: Shigeo
authors.initials: S
authors.lastname: Hayashi
authors.forename: Leo
authors.initials: L
authors.lastname: Tsuda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C500129:chn protein, Drosophila; C063577:emc protein, Drosophila; C489235:hairy protein, Drosophila