Yi Zhang - 5mC Oxidation and Beyond

Reversibility of DNA methylation had been a long sought-after question in the field of epigenetics. Zhang talked about how his team approached the question and showed how the Tet proteins oxidize 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylmethylcytosine (5caC). Importantly, they showed that Tet3 protein is mainly involved in oxidizing paternal 5mC in zygotes, and Tet1 protein can activate meiotic genes during meiosis as well as erase genomic imprinting in primordial germ cells. Zhang also talked about their recent work in the hematopoietic stem cells (HSCs) during aging. They find that old HSCs are heterogeneous and generate more CD150 high population. The CD150 high HSC population is functionally defect in long-term to short-term HSCs differentiation, resulting in a deterioration of the organism's functionality. In summary, CD150 serves as a biomarker, indicating an individual's "epigenetic age”. This observation offers an epigenetic explanation for the phenomenon where older mice can be rejuvenated after receiving HSCs from young mice.