Control of developmentally primed erythroid genes by combinatorial co-repressor actions
- PMID: 26593974
- PMCID: PMC4673834
- DOI: 10.1038/ncomms9893
Control of developmentally primed erythroid genes by combinatorial co-repressor actions
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.
Figures







Similar articles
-
Distinct Ldb1/NLI complexes orchestrate γ-globin repression and reactivation through ETO2 in human adult erythroid cells.Blood. 2011 Dec 1;118(23):6200-8. doi: 10.1182/blood-2011-06-363101. Epub 2011 Oct 18. Blood. 2011. PMID: 22010104 Free PMC article.
-
ETO-2 associates with SCL in erythroid cells and megakaryocytes and provides repressor functions in erythropoiesis.Mol Cell Biol. 2005 Dec;25(23):10235-50. doi: 10.1128/MCB.25.23.10235-10250.2005. Mol Cell Biol. 2005. PMID: 16287841 Free PMC article.
-
Embryonic erythropoiesis and hemoglobin switching require transcriptional repressor ETO2 to modulate chromatin organization.Nucleic Acids Res. 2020 Oct 9;48(18):10226-10240. doi: 10.1093/nar/gkaa736. Nucleic Acids Res. 2020. PMID: 32960220 Free PMC article.
-
Ldb1 complexes: the new master regulators of erythroid gene transcription.Trends Genet. 2014 Jan;30(1):1-9. doi: 10.1016/j.tig.2013.10.001. Epub 2013 Nov 27. Trends Genet. 2014. PMID: 24290192 Free PMC article. Review.
-
Probing the onset and regulation of erythroid cell-specific gene expression.Mt Sinai J Med. 2005 Sep;72(5):333-8. Mt Sinai J Med. 2005. PMID: 16184297 Review.
Cited by
-
IRF2BP2 transcriptional repressor restrains naive CD4 T cell activation and clonal expansion induced by TCR triggering.J Leukoc Biol. 2016 Nov;100(5):1081-1091. doi: 10.1189/jlb.2A0815-368R. Epub 2016 Jun 10. J Leukoc Biol. 2016. PMID: 27286791 Free PMC article.
-
New variant of acute promyelocytic leukemia with IRF2BP2-RARA fusion.Cancer Sci. 2016 Aug;107(8):1165-8. doi: 10.1111/cas.12970. Cancer Sci. 2016. PMID: 27193600 Free PMC article.
-
Erythroid Cell Research: 3D Chromatin, Transcription Factors and Beyond.Int J Mol Sci. 2022 May 30;23(11):6149. doi: 10.3390/ijms23116149. Int J Mol Sci. 2022. PMID: 35682828 Free PMC article. Review.
-
Zebrafish sin3b mutants are viable but have size, skeletal, and locomotor defects.Dev Dyn. 2017 Nov;246(11):946-955. doi: 10.1002/dvdy.24581. Epub 2017 Sep 25. Dev Dyn. 2017. PMID: 28850761 Free PMC article.
-
Splicing factor SF3B1K700E mutant dysregulates erythroid differentiation via aberrant alternative splicing of transcription factor TAL1.PLoS One. 2017 May 18;12(5):e0175523. doi: 10.1371/journal.pone.0175523. eCollection 2017. PLoS One. 2017. PMID: 28545085 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous