The Ash2l SDI Domain Is Required to Maintain the Stability and Binding of DPY30
Mengjie Ma,
Jiafeng Zhou,
Zhihua Ma,
Hanxue Chen,
Liang Li,
Lin Hou,
Bin Yin,
Boqin Qiang,
Pengcheng Shu,
Xiaozhong Peng
Affiliations
Mengjie Ma
The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China
Jiafeng Zhou
The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China
Zhihua Ma
The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China
Hanxue Chen
The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China
Liang Li
The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China
Lin Hou
The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China
Bin Yin
The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China
Boqin Qiang
The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China
Pengcheng Shu
The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China
Xiaozhong Peng
The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primate Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China
ASH2L and DPY30 are important for the assembly and catalytic activity of the complex associated with SET1 (COMPASS), which catalyzes histone methylation and regulates gene expression. However, the regulations among COMPASS components are not fully understood. Here, we leveraged a mouse model and cell lines to observe the outcome of Ash2l depletion and found a significant decrease in DPY30. Analyzing ASH2L ChIP-seq and RNA-seq data excluded transcriptional and translational regulation of ASH2L to DPY30. The decrease in DPY30 was further attributed to the degradation via the ubiquitin-mediated proteasomal pathway. We also verified that three amino acids in the ASH2L Sdc1 DPY30 interaction (SDI) domain are essential for the recognition and binding of DPY30. Lastly, we unexpectedly observed that overexpression of DPY30 in Ash2l-depleted cells rescued the decrease in Ccnd1 and the abnormal cell cycle, which indicates that DPY30 can participate in other complexes to regulate gene expression. Overall, our results, for the first time, reveal that the existence of DPY30 relies on the binding with ASH2L, with degradation of DPY30 via the ubiquitin-proteasome system, and they further indicate that the function of DPY30 can be independent of ASH2L.
