Identification of genes regulated by transcription factor KLF7 in differentiating olfactory sensory neurons.
Gene targeting in mice has recently demonstrated that transcription factor KLF7 plays a critical role in neurite outgrowth and neuronal survival. Here we extended this genetic evidence by establishing the transcriptional profile of differentiating olfactory sensory neurons (OSNs) in Klf7(-/-) mice, and by identifying relevant genes that are directly regulated by KLF7. Functional clustering of DNA microarray data revealed that loss of KLF7 affects primarily the activity of genes involved in OSN differentiation, axonal growth, cytoskeletal dynamics, cell adhesion and synaptogenesis. Cell transfection experiments, on the other hand, demonstrated that the promoters of the genes encoding the OSN-specific OMP and the adhesion molecule L1 are both activated by KLF7 binding to CACCC motifs. Collectively, these results advance knowledge of transcriptional regulation of olfactory neurogenesis and KLF7 action.
Kajimura
Daisuke
D
Child Health Institute of New Jersey, UMDNJ-Robert Wood Johnson Medical School, 89 French Street, New Brunswick, NJ 08901, United States.
Dragomir
Cecilia
C
Ramirez
Francesco
F
Laub
Friedrich
F
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D019922:GAP-43 Protein / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics; D051842:Olfactory Marker Protein / Q000235:genetics; D009831:Olfactory Mucosa / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014158:Transcription, Genetic; D014162:Transfection
D019922:GAP-43 Protein; C426008:Klf7 protein, mouse; D051741:Kruppel-Like Transcription Factors; D039842:Neural Cell Adhesion Molecule L1; D051842:Olfactory Marker Protein; C497598:Omp protein, mouse