Proteomic analysis of FOXP proteins reveals interactions between cortical transcription factors associated with neurodevelopmental disorders
| العنوان: | Proteomic analysis of FOXP proteins reveals interactions between cortical transcription factors associated with neurodevelopmental disorders |
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| المؤلفون: | Marti Quevedo, Raymond A. Poot, Simon E. Fisher, Sara Busquets Estruch, Pelagia Deriziotis, Elliot Sollis, Dick H. W. Dekkers, Arianna Vino, Jeroen Demmers, Sarah A. Graham |
| المساهمون: | Cell biology, Biochemistry |
| المصدر: | Human Molecular Genetics Human Molecular Genetics, 27, 7, pp. 1212-1227 Human Molecular Genetics, 27(7), 1212-1227. Oxford University Press Human Molecular Genetics, 27, 1212-1227 |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Neuroinformatics, Biology, Interactome, 03 medical and health sciences, Purkinje Cells, 0302 clinical medicine, Gene expression, Genetics, Humans, Transcription factor, Molecular Biology, Genetics (clinical), Regulation of gene expression, YY1, FOXP2, Forkhead Transcription Factors, FOXP1, SATB1, General Medicine, Cell biology, Repressor Proteins, 030104 developmental biology, HEK293 Cells, Gene Expression Regulation, Neurodevelopmental Disorders, 030217 neurology & neurosurgery, Transcription Factors |
| الوصف: | FOXP transcription factors play important roles in neurodevelopment, but little is known about how their transcriptional activity is regulated. FOXP proteins cooperatively regulate gene expression by forming homo- and hetero-dimers with each other. Physical associations with other transcription factors might also modulate the functions of FOXP proteins. However, few FOXP-interacting transcription factors have been identified so far. Therefore, we sought to discover additional transcription factors that interact with the brain-expressed FOXP proteins, FOXP1, FOXP2 and FOXP4, through affinity-purifications of protein complexes followed by mass spectrometry. We identified seven novel FOXP-interacting transcription factors (NR2F1, NR2F2, SATB1, SATB2, SOX5, YY1 and ZMYM2), five of which have well-estabslished roles in cortical development. Accordingly, we found that these transcription factors are co-expressed with FoxP2 in the deep layers of the cerebral cortex and also in the Purkinje cells of the cerebellum, suggesting that they may cooperate with the FoxPs to regulate neural gene expression in vivo. Moreover, we demonstrated that etiological mutations of FOXP1 and FOXP2, known to cause neurodevelopmental disorders, severely disrupted the interactions with FOXP-interacting transcription factors. Additionally, we pinpointed specific regions within FOXP2 sequence involved in mediating these interactions. Thus, by expanding the FOXP interactome we have uncovered part of a broader neural transcription factor network involved in cortical development, providing novel molecular insights into the transcriptional architecture underlying brain development and neurodevelopmental disorders. |
| وصف الملف: | application/pdf |
| تدمد: | 0964-6906 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::63a0e1fca9b6d5beda4bc2e0ea8f38fd https://doi.org/10.1093/hmg/ddy035 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....63a0e1fca9b6d5beda4bc2e0ea8f38fd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09646906 |
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