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  Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis.

Rossmann, M. P., Hoi, K., Chan, V., Abraham, B. J., Yang, S., Mullahoo, J., et al. (2021). Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis. Science, 372(6543), 716-721. doi:10.1126/science.aaz2740.

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© 2021 The Authors, exclusive licensee American Association for the Advancement of Science.

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 Creators:
Rossmann, Marlies P. , Author
Hoi, Karen, Author
Chan, Victoria, Author
Abraham, Brian J., Author
Yang, Song, Author
Mullahoo, James , Author
Papanastasiou, Malvina , Author
Wang, Ying, Author
Elia, Ilaria, Author
Perlin, Julie R. , Author
Hagedorn, Elliott J. , Author
Hetzel, Sara1, Author              
Weigert, Raha1, Author              
Vyas, Sejal , Author
Nag, Partha P. , Author
Sullivan, Lucas B., Author
Warren, Curtis R. , Author
Dorjsuren, Bilguujin , Author
Custo Greig, Eugenia , Author
Adatto, Isaac , Author
Cowan, Chad A. , AuthorSchreiber, Stuart L. , AuthorYoung, Richard A. , AuthorMeissner, Alexander1, 2, 3, Author              Haigis, Marcia C., AuthorHekimi, Siegfried, AuthorCarr, Steven A., AuthorZon, Leonard I. , Author more..
Affiliations:
1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              
2Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 01238, USA, ou_persistent22              
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA, ou_persistent22              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2021-03-292021-05-14
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1126/science.aaz2740
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Title: Science
  Abbreviation : Science
Source Genre: Journal
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Publ. Info: Washington, D.C. : American Association for the Advancement of Science
Pages: 6 Volume / Issue: 372 (6543) Sequence Number: - Start / End Page: 716 - 721 Identifier: ISSN: 0036-8075 (print) 1095-9203 (online)
CoNE: https://pure.mpg.de/cone/journals/resource/991042748276600_1