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| Status |
Public on Jan 22, 2019 |
| Title |
TET2 binding to enhancers facilitates transcription factor recruitment in hematopoietic cells [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 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 provide a compelling example of how epigenetic dysregulation can affect gene expression patterns and drive disease development.
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| Overall design |
RNA-seq analysis of hematopoietic cells with and without full-length TET2
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| Contributor(s) |
Rasmussen KD, Berest I, Kessler S, Nishimura K, Simón-Carrasco L, Vassiliou GS, Pedersen MT, Christensen J, Zaugg JB, Helin K |
| Citation(s) |
30796038 |
| Submission date |
Jun 18, 2018 |
| Last update date |
Feb 26, 2019 |
| Contact name |
Kasper Dindler Rasmussen |
| E-mail(s) |
k.d.rasmussen@dundee.ac.uk
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| Organization name |
School of Life Sciences, University of Dundee
|
| Department |
Centre for Gene Regulation & Expression (GRE)
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| Street address |
Dow Street
|
| City |
Dundee |
| ZIP/Postal code |
DD1 5EH |
| Country |
United Kingdom |
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| Platforms (1) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE115972 |
TET2 binding to enhancers facilitates transcription factor recruitment in hematopoietic cells |
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| Relations |
| BioProject |
PRJNA476606 |
| SRA |
SRP150787 |
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