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| Status |
Public on Jun 09, 2021 |
| Title |
Transcriptionally regulated energy metabolism drives early erythropoiesis (mon RNA-seq) |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Transcription and metabolism both influence cell function yet dedicated transcriptional control of metabolic pathways that regulate cell fate has rarely been defined. Through a chemical suppressor screen, we discovered that inhibition of the pyrimidine biosynthesis enzyme DHODH rescues erythroid differentiation in bloodless moonshine mutant embryos defective for the transcription elongation factor tif1γ. This rescue depends on the functional link of DHODH to mitochondrial respiration. Low α-ketoglutarate levels caused by tif1γ loss lead to histone hypermethylation. TIFγ directly controls coenzyme Q synthesis gene expression and coenzyme Q levels are reduced in moonshine mutants. A coenzyme Q analogue rescues moonshine’s bloodless phenotype. These results demonstrate 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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| Overall design |
Heterozygous mon;drl:eGFP fish were crossed with heterozygous mon fish, ensuring transmission of only one allele of drl:EGFP and embryos sorted for green fluorescence (which is markedly reduced in mon mutant embryos) beginning at ~21 hpf. 30 phenotypically mon and wild-type embryos were harvested per replicate (= clutch, each clutch from one pairwise mating) for RNA-seq by homogenizing in TRIzol.
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| Contributor(s) |
Rossmann MP, Yang S, Zon LI |
| Citation(s) |
33986176 |
| |
| Submission date |
Dec 17, 2020 |
| Last update date |
Jun 09, 2021 |
| Contact name |
Leonard Zon |
| E-mail(s) |
zon@enders.tch.harvard.edu
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| Organization name |
Boston Children's Hospital
|
| Department |
Oncology/Hematology
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| Street address |
1 Blackfan Circle
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL21741 |
Illumina HiSeq 4000 (Danio rerio) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE136456 |
Transcriptionally regulated energy metabolism drives early erythropoiesis |
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| Relations |
| BioProject |
PRJNA686152 |
| SRA |
SRP298388 |
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