title: The differential regulation of Gap43 gene in the neuronal differentiation of P19 cells.
abstract: Growth associated protein 43 (Gap43) is a neuron-specific phosphoprotein, which plays critical role in axon growth and synapses functions during neurogenesis. Here we identified two transcription start sites (TSSs) of the mouse Gap43 gene designated as a proximal site at +1, and a distal TSS at -414. RT-qPCR data reveal that the transcripts from +1 increase 10-fold on day-1 post-all-trans retinoic acid (RA) treatment, reached a peak value at day-4 and gradually reduced. By contrast, the distal TSS directs a late, remarkably sharp increase of the transcripts from the day-5 on. An intense signal of Gap43 at the neurites and neural network is determined by the efficient transcription of the distal promoter as shown in Northern blot and RT-qPCR assay. In addition, the targeting of p300 in combination with a differential enrichment of Brm to Brg1 change at the distal promoter region of the gene is induced under RA treatment. The over hundreds of GA rich stretches and the GAGAG elements located between the two TSSs may take parts in the differential transcription of the two TSSs of the Gap43. Our findings provide the first evidence on the identification and differential transcription of the two TSSs of the mouse Gap43 gene, and the preferential distribution of their protein products in the specific stages of RA induced P19 differentiation. These data suggest the efficient transcription of the distal promoter of Gap43 is an important mark for the transition of P19 cells from the progenitor stage into neuronal differentiation.
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Ji-cheng
authors.initials: JC
authors.lastname: Zhao
authors.forename: Lang-xi
authors.initials: LX
authors.lastname: Zhang
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yu-fei
authors.initials: YF
authors.lastname: Shen
mesh_terms: D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000378:metabolism; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D019922:GAP-43 Protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; C499503:Smarca2 protein, mouse; D014157:Transcription Factors; D014212:Tretinoin; D050880:p300-CBP Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases