Control of developmentally primed erythroid genes by combinatorial co-repressor actions
Author(s)
Type
Journal Article
Abstract
How transcription factors (TFs) cooperate within large protein complexes to allow rapid modulation of gene expression during development is still largely unknown. Here we show that the key haematopoietic LIM-domain-binding protein-1 (LDB1) TF complex contains several activator and repressor components that together maintain an erythroid-specific gene expression programme primed for rapid activation until differentiation is induced. A combination of proteomics, functional genomics and in vivo studies presented here identifies known and novel co-repressors, most notably the ETO2 and IRF2BP2 proteins, involved in maintaining this primed state. The ETO2–IRF2BP2 axis, interacting with the NCOR1/SMRT co-repressor complex, suppresses the expression of the vast majority of archetypical erythroid genes and pathways until its decommissioning at the onset of terminal erythroid differentiation. Our experiments demonstrate that multimeric regulatory complexes feature a dynamic interplay between activating and repressing components that determines lineage-specific gene expression and cellular differentiation.
Date Issued
2015-11-23
Date Acceptance
2015-10-14
Citation
Nature Communications, 2015, 6
ISSN
2041-1723
Publisher
Nature Publishing Group
Journal / Book Title
Nature Communications
Volume
6
Copyright Statement
This work is licensed under a Creative Commons Attribution 4.0
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article are included in the article’s Creative Commons license, unless indicated otherwise
in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material.
To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
International License. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise
in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material.
To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
License URL
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
SELECTIVELY MODULATES APOPTOSIS
ACUTE MEGAKARYOBLASTIC LEUKEMIA
INTERFERON REGULATORY FACTOR-2
BREAST-CANCER CELLS
TRANSCRIPTION FACTORS
COMPLEXES FUNCTION
CHIP-SEQ
DIFFERENTIATION
GENOME
ERYTHROPOIESIS
Publication Status
Published
Article Number
8893