Article open access publication

TET2 binding to enhancers facilitates transcription factor recruitment in hematopoietic cells

Genome Research, Cold Spring Harbor Laboratory, ISSN 1088-9051

Volume 29, 4, 2019

DOI:10.1101/gr.239277.118, Dimensions: pub.1112312983, PMC: PMC6442383, PMID: 30796038,



  1. (1) University of Copenhagen, grid.5254.6, KU
  2. (2) European Molecular Biology Institute, Structural and Computational Unit, 69115 Heidelberg, Germany;
  3. (3) Memorial Sloan Kettering Cancer Center, grid.51462.34
  4. (4) Cambridge University Hospitals NHS Foundation Trust, grid.24029.3d
  5. (5) Wellcome Sanger Institute, grid.10306.34


The epigenetic regulator TET2 is frequently mutated in hematological diseases. Mutations have been shown to arise in hematopoietic stem cells early in disease development and lead to altered DNA methylation landscapes and 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 provide evidence that loss of TET2 leads to attenuation of chromatin binding of members of the basic helix-loop-helix (bHLH) TF family. Together, these findings demonstrate that TET2 activity shapes the local chromatin environment at enhancers to facilitate TF binding and provides an example of how epigenetic dysregulation can affect gene expression patterns and drive disease development.


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