Control of developmentally primed erythroid genes by combinatorial co-repressor actions
| Autor: | Stadhouders, Ralph, Cico, Alba, Stephen, Tharshana, Thongjuea, Supat, Kolovos, Petros, Baymaz, H. Irem, Yu, Xiao, Demmers, Jeroen, Bezstarosti, Karel, Maas, Alex, Barroca, Vilma, Kockx, Christel, Ozgur, Zeliha, van Ijcken, Wilfred, Arcangeli, Marie-Laure, Andrieu-Soler, Charlotte, Lenhard, Boris, Grosveld, Frank, Soler, Eric |
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| Přispěvatelé: | Erasmus University Medical Center [Rotterdam] (Erasmus MC), Stabilité génétique, Cellules Souches et Radiations (SCSR (U_967)), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Computational Biology Unit [Bergen] (CBU), University of Bergen (UiB), Computational Regulatory Genomics, Imperial College London, Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cell biology, Developmental Biology, Biochemistry, Molecular Genetics, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Cellules Souches et Radiations (SCSR (U967 / UMR-E_008)), Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Computational Biology Unit, Bergen Center for Computational Science, University of Bergen (UIB), Service Cellules Souches et Radiation (SCSR), Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
[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 |
| Zdroj: | 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⟩ |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms9893⟩ |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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