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

• DOI: 10.1126/science.aaz2740
• Publication Date: 2021-05-13T19:15:35Z
• Authors: Marlies P. Rossmann; Karen Hoi; Victoria Chan; Brian J. Abraham; Song Yang; James Mullahoo; Malvina Papanasta...; 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
• Keywords: 0301 basic medicine; Oxidoreductases Acting on CH-CH Group Donors; Embryo, Nonmammalian; Transcription, Genetic; Ubiquinone; Citric Acid Cycle; Dihydroorotate Dehydrogenase; DNA Methylation; Methylation; Mitochondria; Electron Transport; Histones; 03 medical and health sciences; Oxygen Consumption; Gene Expression Regulation; Animals; Erythropoiesis; Enzyme Inhibitors; Leflunomide; Metabolic Networks and Pathways; Zebrafish; Transcription Factors

Metabolic pathway regulates cell fate

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