biostudies-literatureZou ZNHLBI NIH HHSNHGRI NIH HHSNCI NIH HHS986-994https://www.ebi.ac.uk/biostudies/studies/S-EPMC11499264biostudies-literatureUnknown634(8035)Mutation of tet methylcytosine dioxygenase 2 (encoded by TET2) drives myeloid malignancy initiation and progression^1-3. TET2 deficiency is known to cause a globally opened chromatin state and activation of genes contributing to aberrant haematopoietic stem cell self-renewal^4,5. However, the open chromatin observed in TET2-deficient mouse embryonic stem cells, leukaemic cells and haematopoietic stem and progenitor cells⁵ is inconsistent with the designated role of DNA 5-methylcytosine oxidation of TET2. Here we show that chromatin-associated retrotransposon RNA 5-methylcytosine (m⁵C) can be recognized by the methyl-CpG-binding-domain protein MBD6, which guides deubiquitination of nearby monoubiquitinated Lys119 of histone H2A (H2AK119ub) to promotNatureRNA m<sup>5</sup>C oxidation by TET2 regulates chromatin state and leukaemogenesis.PMC11499264R01 HL145883R01 HL146664R01 CA285299R01 HL174477RM1 HG008935Gao BHe CXu MHong JXiao YSun CLiu QWang HWang JDou XZou ZLi YYang FCZhao LZhang ZDai QWang YYu XfalseRNA m<sup>5</sup>C oxidation by TET2 regulates chromatin state and leukaemogenesis.Mutation of tet methylcytosine dioxygenase 2 (encoded by TET2) drives myeloid malignancy initiation and progression^1-3. TET2 deficiency is known to cause a globally opened chromatin state and activation of genes contributing to aberrant haematopoietic stem cell self-renewal^4,5. However, the open chromatin observed in TET2-deficient mouse embryonic stem cells, leukaemic cells and haematopoietic stem and progenitor cells⁵ is inconsistent with the designated role of DNA 5-methylcytosine oxidation of TET2. Here we show that chromatin-associated retrotransposon RNA 5-methylcytosine (m⁵C) can be recognized by the methyl-CpG-binding-domain protein MBD6, which guides deubiquitination of nearby monoubiquitinated Lys119 of histone H2A (H2AK119ub) to promot2024-01-01T00:00:00Z2024 Oct2026-07-15T08:04:06.719Z2025-04-04T23:32:25.855ZS-EPMC114992643935850610.1038/s41586-024-07969-x