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

被引：80

作者：

Gillespie, Mark A. ^{[1
]}

Palii, Carmen G. ^{[2
,3
]}

Sanchez-Taltavull, Daniel ^{[2
,3
,4
]}

Shannon, Paul ^{[1
]}

Longabaugh, William J. R. ^{[1
]}

Downes, Damien J. ^{[5
]}

Sivaraman, Karthi ^{[2
]}

Espinoza, Herbert M. ^{[1
]}

Hughes, Jim R. ^{[5
]}

Price, Nathan D. ^{[1
]}

Perkins, Theodore J. ^{[2
,3
]}

Ranish, Jeffrey A. ^{[1
,6
]}

Brand, Marjorie ^{[2
,3
]}

机构：

[1] Inst Syst Biol, Seattle, WA 98109 USA

[2] Ottawa Hosp Res Inst, Sprott Ctr Stem Cell Res, Ottawa, ON K1H 8L6, Canada

[3] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8L6, Canada

[4] Univ Bern, Bern Univ Hosp, Dept BioMed Res, Visceral Surg & Med,Inselspital, Murtenstr 35, CH-3008 Bern, Switzerland

[5] Univ Oxford, Weatherall Inst Mol Med, Radcliffe Dept Med, MRC,Mol Haematol Unit, Oxford OX3 9DS, Oxford OX3 9DS, England

[6] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

来源：

MOLECULAR CELL | 2020年 / 78卷 / 05期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

HEMATOPOIETIC STEM-CELLS; STATISTICAL-MODEL; MASS-SPECTROMETRY; NETWORK CONTROL; READ ALIGNMENT; PROTEINS; LINEAGE; CHROMATIN; TANDEM; COMMITMENT;

D O I：

10.1016/j.molcel.2020.03.031

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：960 / +

页数：26

共 87 条

[1] Widespread and dynamic translational control of red blood cell development [J].