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ETV2 primes hematoendothelial gene enhancers prior to hematoendothelial fate commitment.

Cell reports | 2023

Mechanisms underlying distinct specification, commitment, and differentiation phases of cell fate determination remain undefined due to difficulties capturing these processes. Here, we interrogate the activity of ETV2, a transcription factor necessary and sufficient for hematoendothelial differentiation, within isolated fate intermediates. We observe transcriptional upregulation of Etv2 and opening of ETV2-binding sites, indicating new ETV2 binding, in a common cardiac-hematoendothelial progenitor population. Accessible ETV2-binding sites are active at the Etv2 locus but not at other hematoendothelial regulator genes. Hematoendothelial commitment coincides with the activation of a small repertoire of previously accessible ETV2-binding sites at hematoendothelial regulators. Hematoendothelial differentiation accompanies activation of a large repertoire of new ETV2-binding sites and upregulation of hematopoietic and endothelial gene regulatory networks. This work distinguishes specification, commitment, and sublineage differentiation phases of ETV2-dependent transcription and suggests that the shift from ETV2 binding to ETV2-bound enhancer activation, not ETV2 binding to target enhancers, drives hematoendothelial fate commitment.

Pubmed ID: 37330911 RIS Download

Associated grants

  • Agency: NHLBI NIH HHS, United States
    Id: T32 HL139430
  • Agency: NIA NIH HHS, United States
    Id: R21 AG054770
  • Agency: NHLBI NIH HHS, United States
    Id: T32 HL007381
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK119621
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL055337
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007197
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL163523
  • Agency: NICHD NIH HHS, United States
    Id: R01 HD111938
  • Agency: NHLBI NIH HHS, United States
    Id: F32 HL156465
  • Agency: NHLBI NIH HHS, United States
    Id: F30 HL131298
  • Agency: NHLBI NIH HHS, United States
    Id: P01 HL146366
  • Agency: NIA NIH HHS, United States
    Id: R33 AG054770
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL147571
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007183
  • Agency: NHGRI NIH HHS, United States
    Id: R21 HG012423

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