TET2 binding to enhancers facilitates transcription factor recruitment in hematopoietic cells Journal Article

   


Authors: Rasmussen, K. D.; Berest, I.; Keβler, S.; Nishimura, K.; Simón-Carrasco, L.; Vassiliou, G. S.; Pedersen, M. T.; Christensen, J.; Zaugg, J. B.; Helin, K.
Article Title: TET2 binding to enhancers facilitates transcription factor recruitment in hematopoietic cells
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 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. © 2019 Rasmussen et al.
Keywords: controlled study; ten eleven translocation 3; unclassified drug; promoter region; nonhuman; animal cell; mouse; gene targeting; gene expression; embryonic stem cell; protein depletion; signal noise ratio; genome-wide association study; transcription factor; cell differentiation; dna methylation; gene mapping; dna; chromatin; chromatin immunoprecipitation; cpg island; binding site; hematopoietic stem cell; transcription factor gata 1; kruppel like factor 4; basic helix loop helix transcription factor; enhancer region; transcription factor runx1; 5 methylcytosine; cross linking; plasmacytoid dendritic cell; acute myeloid leukemia; high throughput sequencing; 5 hydroxymethylcytosine; dioxygenase; priority journal; article; clustered regularly interspaced short palindromic repeat; genetic profile
Journal Title: Genome Research
Volume: 29
Issue: 4
ISSN: 1088-9051
Publisher: Cold Spring Harbor Laboratory Press  
Date Published: 2019-04-01
Start Page: 564
End Page: 575
Language: English
DOI: 10.1101/gr.239277.118
PUBMED: 30796038
PROVIDER: scopus
PMCID: PMC6442383
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85063984040&doi=10.1101%2fgr.239277.118&partnerID=40&md5=1cd5a2bab8b8f8ab9f272a19fb91aa49
Notes: Article -- Export Date: 1 May 2019 -- Source: Scopus
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MSK Authors
  1. Kristian Helin
    33 Helin
  2. Koutarou Nishimura
    3 Nishimura
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