The role of transcriptional corepressor Nif3l1 in early stage of neural differentiation via cooperation with Trip15/CSN2.
Mouse Nif3l1 gene is highly conserved from bacteria to human. Even though this gene is expressed throughout embryonic development, its biological function is still obscure. Here, we show that Nif3l1 participates in retinoic acid-primed neural differentiation of P19 embryonic carcinoma cells through cooperation with Trip15/CSN2, a transcriptional corepressor/component of COP9 signalosome. We isolated Nif3l1 cDNA from P19 cell cDNA library by a yeast two-hybrid screening using Trip15/CSN2 as a bait. This interaction was confirmed by a pull-down assay and an epitope-tagged coimmunoprecipitation. Although Nif3l1 was mainly detected in the cytoplasm, the translocation of Nif3l1 into the nuclei was observed in retinoic acid-primed neural differentiation of P19 cells and enhanced by the enforced expression of Trip15/CSN2. Furthermore, enforced expression of sense Nif3l1 RNA, but not antisense RNA, enhanced the neural differentiation of P19 cells accompanying the intense down-regulation of Oct-3/4 mRNA expression and the rapid induction of Mash-1 mRNA expression. Luciferase reporter assay showed that Nif3l1 could act as a transcriptional repressor and synergized the transcriptional repression by Trip15/CSN2. These results indicate that Nif3l1 implicates in neural differentiation through the cooperation with Trip15/CSN2.
Akiyama
Hirotada
H
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Yamazaki, Noda-shi, Chiba 278-8510, Japan.
Fujisawa
Naoko
N
Tashiro
Yousuke
Y
Takanabe
Natsuko
N
Sugiyama
Akinori
A
Tashiro
Fumio
F
D000595:Amino Acid Sequence; D000818:Animals; D000075686:COP9 Signalosome Complex; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D011988:Receptors, Thyroid Hormone / Q000737:chemistry / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
D056970:Co-Repressor Proteins; C118919:Cops2 protein, mouse; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; C486006:Nif3l1 protein, mouse; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D011506:Proteins; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors; D000075686:COP9 Signalosome Complex