Academic Journal
Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis.
| العنوان: | Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis. |
|---|---|
| المؤلفون: | Rossmann, M., Hoi, K., Chan, V., Abraham, B., Yang, S., Mullahoo, J., Papanastasiou, M., Wang, Y., Elia, I., Perlin, J., Hagedorn, E., Hetzel, S., Weigert, R., Vyas, S., Nag, P., Sullivan, L., Warren, C., Dorjsuren, B., Custo Greig, E., Adatto, I., Cowan, C., Schreiber, S., Young, R., Meissner, A., Haigis, M., Hekimi, S., Carr, S., Zon, L. |
| المصدر: | Science |
| سنة النشر: | 2021 |
| المجموعة: | Max Planck Society: MPG.PuRe |
| الوصف: | Transcription and metabolism both influence cell function, but dedicated transcriptional control of metabolic pathways that regulate cell fate has rarely been defined. We discovered, using a chemical suppressor screen, that inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) rescues erythroid differentiation in bloodless zebrafish moonshine (mon) mutant embryos defective for transcriptional intermediary factor 1 gamma (tif1γ). This rescue depends on the functional link of DHODH to mitochondrial respiration. The transcription elongation factor TIF1γ directly controls coenzyme Q (CoQ) synthesis gene expression. Upon tif1γ loss, CoQ levels are reduced, and a high succinate/α-ketoglutarate ratio leads to increased histone methylation. A CoQ analog rescues mon’s bloodless phenotype. These results demonstrate that mitochondrial metabolism is a key output of a lineage transcription factor that drives cell fate decisions in the early blood lineage. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | http://hdl.handle.net/21.11116/0000-0008-AC9D-6; http://hdl.handle.net/21.11116/0000-0008-AC9F-4 |
| الاتاحة: | http://hdl.handle.net/21.11116/0000-0008-AC9D-6 http://hdl.handle.net/21.11116/0000-0008-AC9F-4 |
| Rights: | info:eu-repo/semantics/openAccess ; https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.71BCC2EC |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |