NASP antagonize chromatin accessibility through maintaining histone H3K9me1 in hepatocellular carcinoma

作者：Kang, Xuan; Feng, Yun; Gan, Zhixue; Zeng, Shiyang; Guo, Xiaobo; Chen, Xirui; Zhang, Ye; Wang, Chen; Liu, Kuinan; Chen, Xuelin; Jiang, Xiaoxue; Song, Shuting; Li, Yabin; Chen, Su; Sun, Feng; Mao, Zhiyong; Yang, Xiaomei^*; Chang, Jianfeng^*

来源：Biochimica et Biophysica Acta-Molecular Basis of Disease, 2018, 1864(10): 3438-3448.

DOI：10.1016/j.bbadis.2018.07.033

• NASP
• Liver cancer
• Replication stress
• Transcription
• H3K9me1

The regulation of histone deposits mediated by multi-chaperone complexes under physiological conditions remains to be further investigated. Here, we studied the function of nuclear autoantigenic sperm protein (NASP) in the regulation of liver cancer. We found that NASP levels in liver tumors were generally higher than in normal liver tissues and NASP down-regulation inhibited liver cancer cells from forming tumors. We further analyzed cellular responses and epigenetic mechanisms of the histone H3-H4 shortage induced by NASP knockdown in liver cancer cells. The results showed that the major effects of NASP knockdown were globally enhanced chromatin accessibility, which facilitates transcription release, and failure of replication initiation. Furthermore, we demonstrated that NASP depletion led to a global decrease of histone H3K9me1 modification associated with newly H3 processing, which occurred directly at the promoters of up-regulated anti-tumor genes BACH2 and RunX1T1. This also resulted in a synergistic effect on enhanced apoptosis with Myc and p53 decreases. Overall, our work provides new insights into the roles of NASP in tumorigenesis and cancer prevention.

• 出版日期2018-10
• 单位西安交通大学; 清华大学; 同济大学