NASP antagonize chromatin accessibility through maintaining histone H3K9me1 in hepatocellular carcinoma

Publication date: Available online 1 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Xuan Kang, Yun Feng, Zhixue Gan, Shiyang Zeng, Xiaobo Guo, Xirui Chen, Ye Zhang, Chen Wang, Kuinan Liu, Xuelin Chen, Xiaoxue Jiang, Shuting Song, Yabin Li, Su Chen, Feng Sun, Zhiyong Mao, Xiaomei Yang, Jianfeng ChangAbstractThe 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...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research