4.8 Article

Control of developmentally primed erythroid genes by combinatorial co-repressor actions

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NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -

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NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms9893

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资金

  1. Royal Netherlands Academy of Arts and Sciences (KNAW
  2. 'Academy Assistant' fellowship)
  3. EMBO Long-term Fellowship [ALTF 1201-2014]
  4. Marie Curie Individual Fellowship [H2020-MSCA-IF-2014, 654933]
  5. Marie Curie European Reintegration Grant [FP7-PEOPLE-2010-RG]
  6. CEA/IRTELIS fellowship
  7. EpiGenSys/ERASysBio+/FP7 (NL: NWO, UK: BSRC, D: BMBF)
  8. Bluescript EU Integrated Project
  9. Netherlands Genomics Initiative (MEC Booster grant)
  10. KNAW Academy Professorship
  11. Cancer Genomics Center (NGI, NL)
  12. NIRM (NL)
  13. SyBoSS EU Consortium
  14. FSER (Schlumberger Foundation for Education and Research)
  15. ARC foundation [SFI20121205625]
  16. Atip-Avenir program
  17. MRC [MC_UP_1102/1] Funding Source: UKRI
  18. Marie Curie Actions (MSCA) [654933] Funding Source: Marie Curie Actions (MSCA)
  19. Medical Research Council [MC_UP_1102/1] Funding Source: researchfish

向作者/读者索取更多资源

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.

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