Role for RFX transcription factors in non-neuronal cell-specific inactivation of the microtubule-associated protein MAP1A promoter.
Microtubule-associated protein MAP1A is expressed abundantly in mature neurons and is necessary for maintenance of neuronal morphology and localization of some molecules in association with the microtubule-based cytoskeleton. Previous studies indicated that its complementary expression together with MAP1B during nervous system development is regulated at the transcriptional level and that the mouse Map1A gene is transcribed under the control of 5' and intronic promoters. In this study, we investigated the regulatory mechanisms that govern the neuronal cell-specific activation of the MAP1A 5' promoter. We found that two regulatory factor for X box (RFX) binding sites in exon1 of both the mouse and human genes are important for effective transcriptional repression observed only in non-neuronal cells by reporter assays. Among RFX transcription factor family members, RFX1 and 3 mainly interact with repressive elements in vitro. Cotransfection studies indicated that RFX1, which is expressed ubiquitously, down-regulated the MAP1A 5' promoter activity in non-neuronal cells. Unexpectedly, RFX3, which is abundantly expressed in neuronal cells, down-regulated the transactivity as well, when it was expressed in non-neuronal cells. Both RFX1 and 3 did not down-regulate the transactivity in neuronal cells. These results suggest that RFX1 and 3 are pivotal factors in down-regulation of the MAP1A 5' promoter in non-neuronal cells. The cell type-specific down-regulation, however, does not depend simply on which RFX interacts with the elements, but seems to depend on underlying profound mechanisms.
Nakayama
Atsuo
A
Department of Pathology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Aichi, Japan. k46191a@nucc.cc.nagoya-u.ac.jp
Murakami
Hideki
H
Maeyama
Naomi
N
Yamashiro
Norie
N
Sakakibara
Ayako
A
Mori
Naoyoshi
N
Takahashi
Masahide
M
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005091:Exons; D020868:Gene Silencing; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D000071716:Regulatory Factor X1; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C093429:MAP1A protein, human; C490547:MAP1A protein, mouse; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C000605537:RFX1 protein, human; C000605540:RFX3 protein, human; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D000071701:Regulatory Factor X Transcription Factors; D000071716:Regulatory Factor X1; C000605538:Rfx1 protein, mouse; C000605541:Rfx3 protein, mouse; D014157:Transcription Factors