DNA methylation disruption reshapes the hematopoietic differentiation landscape.

ABSTRACT: Mutations in genes involved in DNA methylation (DNAme; for example, TET2 and DNMT3A) are frequently observed in hematological malignancies^1-3 and clonal hematopoiesis^4,5. Applying single-cell sequencing to murine hematopoietic stem and progenitor cells, we observed that these mutations disrupt hematopoietic differentiation, causing opposite shifts in the frequencies of erythroid versus myelomonocytic progenitors following Tet2 or Dnmt3a loss. Notably, these shifts trace back to transcriptional priming skews in uncommitted hematopoietic stem cells. To reconcile genome-wide DNAme changes with specific erythroid versus myelomonocytic skews, we provide evidence in support of differential sensitivity of transcription factors due to biases in CpG enrichment in their binding

SUBMITTER: Izzo F 

PROVIDER: S-EPMC7216752 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature