Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis-Reference-Cited by-同舟云学术

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

Published:2021-05-14 Issue:6543 Volume:372 Page:716-721
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Rossmann Marlies P.¹²^ORCID,Hoi Karen¹²,Chan Victoria¹²^ORCID,Abraham Brian J.³^ORCID,Yang Song²,Mullahoo James⁴^ORCID,Papanastasiou Malvina⁴^ORCID,Wang Ying⁵,Elia Ilaria⁶^ORCID,Perlin Julie R.²^ORCID,Hagedorn Elliott J.²^ORCID,Hetzel Sara⁷,Weigert Raha⁷^ORCID,Vyas Sejal⁶,Nag Partha P.⁴,Sullivan Lucas B.⁸^ORCID,Warren Curtis R.⁹,Dorjsuren Bilguujin¹²^ORCID,Greig Eugenia Custo¹²,Adatto Isaac¹²^ORCID,Cowan Chad A.⁹,Schreiber Stuart L.⁴^ORCID,Young Richard A.³¹⁰^ORCID,Meissner Alexander¹⁴⁷^ORCID,Haigis Marcia C.⁶^ORCID,Hekimi Siegfried⁵^ORCID,Carr Steven A.⁴^ORCID,Zon Leonard I.¹²^ORCID

Affiliation:

1. Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 01238, USA.

2. Stem Cell Program and Division of Hematology/Oncology, Boston Children’s Hospital and Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.

3. Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

4. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

5. Department of Biology, McGill University, Montréal, Québec H3A 1B1, Canada.

6. Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.

7. Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.

8. Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

9. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

10. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract

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

Funder

National Heart, Lung, and Blood Institute

National Human Genome Research Institute

National Cancer Institute

National Institute of General Medical Sciences

Cancer Research Institute

Canadian Institutes of Health Research

National Institute of Diabetes and Digestive and Kidney Diseases

Harvard Catalyst

American Lebanese Syrian Associated Charities

Publisher

American Association for the Advancement of Science (AAAS)