Edit
Edit
Our work about TET2 function at enhancers in AML is online! – Zaugg Group

Zaugg Group

Systems (epi)genetics to study the basis of complex traits and diseases

Our work about TET2 function at enhancers in AML is online!

Great collaboration with Kasper Rasmussen and Christian Helin! Check it out here: https://genome.cshlp.org/content/29/4/564 

TET2 binding to enhancers facilitates transcription factor recruitment in hematopoietic cells

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.

Edit
Edit