Kinetics and Accuracy of DNA Remethylation in Dnmt3a deficient hematopoietic cells

Mutations in the DNMT3A gene can cause the clonal expansion of hematopoietic stem/progenitor cells. The DNMT3AR882H/C mutation is associated with a focal, canonical DNA hypomethylation phenotype that may be relevant for the development of myeloid malignancies. To determine whether the hypomethylation phenotype caused by Dnmt3a deficiency can be corrected, we used an inducible DNMT3A transgene to restore expression of DNMT3A in transplanted bone marrow cells derived from Dnmt3a-/- mice. Remethylation of hypomethylated regions begins within a week, and is essentially complete within 6 months. Remethylation occurs in an accurate, ordered, dynamic, and canonical fashion, suggesting that not all differentially methylated regions are functionally equivalent.