Preprint open access publication

TET2 binding to enhancers facilitates transcription factor recruitment in hematopoietic cells

bioRxiv, Cold Spring Harbor Laboratory,


DOI:10.1101/336008, Dimensions: pub.1104326112,



  1. (1) University of Dundee, grid.8241.f
  2. (2) University of Copenhagen, grid.5254.6, KU
  3. (3) European Molecular Biology Institute, Structural and Computational Unit, .
  4. (4) Friedrich Miescher Institute, grid.482245.d
  5. (5) Cambridge University Hospitals NHS Foundation Trust, grid.24029.3d
  6. (6) Wellcome Sanger Institute, grid.10306.34




United Kingdom




ABSTRACT The epigenetic regulator TET2 is frequently mutated in hematological diseases. Mutations have been shown to arise in hematopoietic stem cells early in disease development, lead to altered DNA methylation landscapes and to an increased risk of hematopoietic malignancy. Here, we show by genome-wide mapping of TET2 binding sites in different cell types that TET2 localizes to regions of open chromatin and cell-type specific enhancers. We find that deletion of Tet2 in native hematopoiesis as well as fully transformed Acute Myeloid Leukemia (AML) results in changes in transcription factor (TF) activity within these regions, and we demonstrate that loss of TET2 leads to enzymatic activity-dependent attenuation of chromatin binding of the hematopoietic TF CDX4. Together, these findings demonstrate that TET2 activity shapes the local chromatin environment at enhancers to facilitate TF binding and provide a compelling example of how epigenetic dysregulation can affect gene expression patterns and drive disease development.


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