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

doi:10.1126/science.aaz2740

GSTDTAP > 气候变化

DOI	10.1126/science.aaz2740
	Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis
	Marlies P. Rossmann; Karen Hoi; Victoria Chan; Brian J. Abraham; Song Yang; James Mullahoo; Malvina Papanastasiou; Ying Wang; Ilaria Elia; Julie R. Perlin; Elliott J. Hagedorn; Sara Hetzel; Raha Weigert; Sejal Vyas; Partha P. Nag; Lucas B. Sullivan; Curtis R. Warren; Bilguujin Dorjsuren; Eugenia Custo Greig; Isaac Adatto; Chad A. Cowan; Stuart L. Schreiber; Richard A. Young; Alexander Meissner; Marcia C. Haigis; Siegfried Hekimi; Steven A. Carr; Leonard I. Zon
	2021-05-14
发表期刊	Science
出版年	2021
英文摘要	Lineage-specific regulators direct cell fate decisions, but the precise mechanisms are not well known. Using an in vivo chemical suppressor screen of a bloodless zebrafish mutant, Rossmann et al. show that the lineage-specific chromatin factor tif1γ directly regulates mitochondrial genes to drive red blood cell differentiation. Loss of tif1γ reduces coenzyme Q synthesis and function, impeding mitochondrial respiration and leading to epigenetic alterations and repression of erythropoiesis. The loss of blood in the mutant fish can be rescued by the addition of coenzyme Q. This work establishes a mechanism by which a chromatin factor tunes a metabolic pathway in a tissue-specific manner. Science , this issue p. [716][1] 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. [1]: /lookup/doi/10.1126/science.aaz2740
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/326816
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Marlies P. Rossmann,Karen Hoi,Victoria Chan,et al. Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis[J]. Science,2021.
APA	Marlies P. Rossmann.,Karen Hoi.,Victoria Chan.,Brian J. Abraham.,Song Yang.,...&Leonard I. Zon.(2021).Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis.Science.
MLA	Marlies P. Rossmann,et al."Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis".Science (2021).