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Prof. Xuetao Cao’s Group Published New Epigenetic Regulatory Mechanism For Pathogen Infection-Induced Myelopoiesis

 

Prof. Xuetao Cao (Peking Union Medical College, Chinese Academy of Medical Sciences) and his group published a research article in Nature about the new epigenetic regulation mechanism on pathogen infection-induced myelopoiesis (Shen Q, Zhang Q, Shi Y, Shi Q, Jiang Y, Gu Y, Li Z, Li X, Zhao K, Wang C, Li N & Cao X. Tet2 promotes pathogen infection-induced myelopoiesis through mRNA oxidation. Nature. 2018 Feb 1;554(7690):123-127.).

Supported by the grants from National Natural Science Foundation of China and Shanghai Rising-Star Progranm and the CAMS Innovation Fund for Medical Science, Prof. Xuetao Cao, PhD student Qicong Shen and associate professor Qian Zhang demonstrated that Tet2 promoted both abdominal sepsis-induced emergency myelopoiesis and parasite-induced mast cell expansion through decreasing mRNA levels of Socs3, a key negative regulator of the JAK–STAT pathway that is critical for cytokine-induced myelopoiesis. Tet2 repressed Socs3 at post-transcriptional level, implying its potential role as an RNA binding protein. For the underlying mechanism, crosslinking and immunoprecipitation sequencing (CLIP-seq) and bisulfite-sequencing of mRNAs revealed that Tet2 bound to the 3’-UTR of Socs3 mRNA and inhibited the level of cytosine methylation in the region which might influence dsRNA formation at 3`-UTR of Socs3, thus promoted the degradation of Socs3 mRNA.

This work reveals a previously unknown regulatory role of Tet2 at post-transcription level, and also promoting myelopoiesis during infection at an immunological view. It provides new ideas and potential drug development targets for effective prevention and treatment of infectious diseases. Moreover, inhibitory function of cytosine methylation repressed by Tet2 in mRNAs reveals its new physiological role in mammalian system.