Absolute Quantification of Transcription Factors Reveals Principles of Gene Regulation in Erythropoiesis.

Gillespie, Mark A; Palii, Carmen G; Sanchez-Taltavull, Daniel; Shannon, Paul; Longabaugh, William J R; Downes, Damien J; Sivaraman, Karthi; Espinoza, Herbert M; Hughes, Jim R; Price, Nathan D; Perkins, Theodore J; Ranish, Jeffrey A; Brand, Marjorie (2020). Absolute Quantification of Transcription Factors Reveals Principles of Gene Regulation in Erythropoiesis. Molecular cell, 78(5), 960-974.e11. Cell Press 10.1016/j.molcel.2020.03.031

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Dynamic cellular processes such as differentiation are driven by changes in the abundances of transcription factors (TFs). However, despite years of studies, our knowledge about the protein copy number of TFs in the nucleus is limited. Here, by determining the absolute abundances of 103 TFs and co-factors during the course of human erythropoiesis, we provide a dynamic and quantitative scale for TFs in the nucleus. Furthermore, we establish the first gene regulatory network of cell fate commitment that integrates temporal protein stoichiometry data with mRNA measurements. The model revealed quantitative imbalances in TFs' cross-antagonistic relationships that underlie lineage determination. Finally, we made the surprising discovery that, in the nucleus, co-repressors are dramatically more abundant than co-activators at the protein level, but not at the RNA level, with profound implications for understanding transcriptional regulation. These analyses provide a unique quantitative framework to understand transcriptional regulation of cell differentiation in a dynamic context.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine

UniBE Contributor:

Sánchez Taltavull, Daniel

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1097-2765

Publisher:

Cell Press

Language:

English

Submitter:

Rahel Fuhrer

Date Deposited:

21 Dec 2020 08:39

Last Modified:

05 Dec 2022 15:42

Publisher DOI:

10.1016/j.molcel.2020.03.031

PubMed ID:

32330456

Uncontrolled Keywords:

absolute quantification cell fate erythropoiesis gene regulatory network hematopoiesis protein stoichiometry proteomics stem cells targeted mass spectrometry transcription

BORIS DOI:

10.7892/boris.148709

URI:

https://boris.unibe.ch/id/eprint/148709

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