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Control of developmentally primed erythroid genes by combinatorial co-repressor actions
- Source :
- Nature Communications, Nature Communications, Nature Publishing Group, 2015, 6 (1), pp.E5777-E5786. ⟨10.1038/ncomms9893⟩, Nature Communications, 6. Nature Publishing Group, Nature Communications, 2015, 6 (1), pp.E5777-E5786. ⟨10.1038/ncomms9893⟩
- Publication Year :
- 2015
- Publisher :
- Nature Pub. Group, 2015.
-
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.<br />Conserved sets of transcription factors (TFs) regulate hematopoiesis. Here, Stadhouders et al. show that IRF2BP2 is a component of the LDB1 TF complex and together with its co-repressor ETO2, enhances transcriptional repression, which plays a crucial role at the erythroid progenitor stage.
- Subjects :
- [SDV]Life Sciences [q-bio]
Molecular Sequence Data
Article
SELECTIVELY MODULATES APOPTOSIS
Mice
ACUTE MEGAKARYOBLASTIC LEUKEMIA
Erythroid Cells
MD Multidisciplinary
Animals
Humans
Nuclear Receptor Co-Repressor 1
Erythropoiesis
Nuclear Receptor Co-Repressor 2
Amino Acid Sequence
Science & Technology
Base Sequence
Tumor Suppressor Proteins
BREAST-CANCER CELLS
CHIP-SEQ
Gene Expression Regulation, Developmental
Nuclear Proteins
LIM Domain Proteins
Multidisciplinary Sciences
GENOME
DNA-Binding Proteins
Repressor Proteins
DIFFERENTIATION
INTERFERON REGULATORY FACTOR-2
COMPLEXES FUNCTION
Science & Technology - Other Topics
Carrier Proteins
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.pmid.dedup....902b3e09c2133125d768885828d89d49