title: Conserved sequence block clustering and flanking inter-cluster flexibility delineate enhancers that regulate nerfin-1 expression during Drosophila CNS development.
abstract: We have identified clusters of conserved sequences constituting discrete modular enhancers within the Drosophilanerfin-1 locus. nerfin-1 encodes a Zn-finger transcription factor that directs pioneer interneuron axon guidance. nerfin-1 mRNA is detected in many early delaminating neuroblasts, ganglion mother cells and transiently in nascent neurons. The comparative genomics analysis program EvoPrinter revealed conserved sequence blocks both upstream and downstream of the transcribed region. By using the aligning regions of different drosophilids as the reference DNA, EvoPrinter detects sequence length flexibility between clusters of conserved sequences and thus facilitates differentiation between closely associated modular enhancers. Expression analysis of enhancer-reporter transgenes identified enhancers that drive expression in different regions of the developing embryonic and adult nervous system, including subsets of embryonic CNS neuroblasts, GMCs, neurons and PNS neurons. In summary, EvoPrinter facilitates the discovery and analysis of enhancers that control crucial aspects of nerfin-1 expression.
authors.affiliation: Neural Cell-Fate Determinants Section, NINDS, NIH, Bethesda, MD, USA. Alex.Kuzin@ninds.nih.gov
authors.forename: Alexander
authors.initials: A
authors.lastname: Kuzin
authors.forename: Mukta
authors.initials: M
authors.lastname: Kundu
authors.forename: Antonios
authors.initials: A
authors.lastname: Ekatomatis
authors.forename: Thomas
authors.initials: T
authors.lastname: Brody
authors.forename: Ward F
authors.initials: WF
authors.lastname: Odenwald
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002490:Central Nervous System / Q000196:embryology* / Q000378:metabolism; D055028:Comparative Genomic Hybridization; D019295:Computational Biology; D017124:Conserved Sequence; D004330:Drosophila / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004742:Enhancer Elements, Genetic / Q000235:genetics* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D014644:Genetic Variation / Q000502:physiology; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000502:physiology*; D012984:Software; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D014157:Transcription Factors; C418490:nerfin-1 protein, Drosophila