TET2 mutations are associated with hypermethylation at key regulatory enhancers in normal and malignant hematopoiesis

Morten Tulstrup, Mette Soerensen, Jakob Werner Hansen, Linn Gillberg, Maria Needhamsen, Katja Kaastrup, Kristian Helin, Kaare Christensen, Joachim Weischenfeldt () and Kirsten Grønbæk ()
Additional contact information
Morten Tulstrup: Department of Hematology, Rigshospitalet
Mette Soerensen: University of Southern Denmark
Jakob Werner Hansen: Department of Hematology, Rigshospitalet
Linn Gillberg: Department of Hematology, Rigshospitalet
Maria Needhamsen: Karolinska Institutet
Katja Kaastrup: Department of Hematology, Rigshospitalet
Kristian Helin: University of Copenhagen
Kaare Christensen: University of Southern Denmark
Joachim Weischenfeldt: University of Copenhagen
Kirsten Grønbæk: Department of Hematology, Rigshospitalet

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract Mutations in the epigenetic modifier TET2 are frequent in myeloid malignancies and clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). Here, we investigate associations between TET2 mutations and DNA methylation in whole blood in 305 elderly twins, 15 patients with CCUS and 18 healthy controls. We find that TET2 mutations are associated with DNA hypermethylation at enhancer sites in whole blood in CHIP and in both granulocytes and mononuclear cells in CCUS. These hypermethylated sites are associated with leukocyte function and immune response and ETS-related and C/EBP-related transcription factor motifs. While the majority of TET2-associated hypermethylation sites are shared between CHIP and in AML, we find a set of AML-specific hypermethylated loci at active enhancer elements in hematopoietic stem cells. In summary, we show that TET2 mutations is associated with hypermethylated enhancers involved in myeloid differentiation in both CHIP, CCUS and AML patients.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-26093-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26093-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-26093-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().