RT Journal
A1 Rasmussen, Kasper D.
A1 Berest, Ivan
A1 Keβler, Sandra
A1 Nishimura, Koutarou
A1 Simón-Carrasco, Lucía
A1 Vassiliou, George S.
A1 Pedersen, Marianne T.
A1 Christensen, Jesper
A1 Zaugg, Judith B.
A1 Helin, Kristian
T1 TET2 binding to enhancers facilitates transcription factor recruitment in hematopoietic cells
JF Genome Research 
JO Genome Research 
YR 2019 
FD April 01 
VO 29 
IS 4 
SP 564 
OP 575 
DO 10.1101/gr.239277.118 
UL http://genome.cshlp.org/content/29/4/564.abstract 
AB 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.