Researcher Jiekai Chen, Director of Cell Genealogy and Development Research Center, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Executive Deputy Director of the Key Laboratory of Regenerative Biology, Chinese Academy of Sciences, Chief Scientist of National Key Research and Development Program and 973 Program, National Natural Science Excellent Youth, once awarded National Natural Science The Second Prize of Science, Outstanding Achievement Award of Chinese Academy of Sciences and other awards. This talk mainly introduces histone H3K9me3, which is a key epigenetic modification of heterochromatin. Director Chen's team discovered that H3K9me3 is an important obstacle to somatic cell reprogramming. To further study the function of H3K9me3, they found that in mouse embryonic stem cells (mESC), Setdb1 mainly catalyzes the formation of H3K9me3 on retrotransposons and inhibits its expression. Furthermore, they discovered a new mechanism by which RNA m6A recruits SETDB1 through YTHDC1 to regulate retrotransposable elements. Loss of RNA m6A methylase Mettl3 and reader Ythdc1 can cause mouse embryonic death, but the mechanism is unknown. Director Chen’s team discovered that in mESC, RNA transcribed from retrotransposable elements such as IAP and LINE1 bind to protochromatin regions, and m6A on these RNAs recruit YTHDC1 to chromatin, which is extremely important for chromatin localization of SETDB1 and H3K9me3. Similar to SETDB1, IAP and LINE1 were activated after YTHDC1 was knocked out, and H3K9me3 decreased significantly. After knocking out SETDB1 or YTHDC1, due to the activation of the Dux gene silenced by LINE1 RNA, mESC will reprogram into 2C-like cells, changing from pluripotency to pluripotency. Through YTH domain point mutation filling and Mettl3 knockout, they proved that the chromatin regulation mechanism of YTHDC1-SETDB1-H3K9me3 is m6A-dependent. In summary, for the cell fate regulation function of H3K9me3, they clarified the important role of SETDB1 and discovered a new mechanism by which RNA m6A recruits SETDB1 through YTHDC1 to regulate the formation of H3K9me3 heterochromatin, and proved that this is the main factor that restricts the transformation of mESC into 2C-like cells. Epigenetic mechanism.
In the picture is a lively discussion between Director Chen and the teachers of Shenzhen Bay Laboratory.