| Literature DB >> 30076957 |
Xuan Kang1, Yun Feng2, Zhixue Gan1, Shiyang Zeng1, Xiaobo Guo1, Xirui Chen1, Ye Zhang3, Chen Wang1, Kuinan Liu1, Xuelin Chen1, Xiaoxue Jiang1, Shuting Song1, Yabin Li1, Su Chen4, Feng Sun1, Zhiyong Mao1, Xiaomei Yang5, Jianfeng Chang6.
Abstract
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.Entities:
Keywords: H3K9me1; Liver cancer; NASP; Replication stress; Transcription
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Year: 2018 PMID： 30076957 DOI： 10.1016/j.bbadis.2018.07.033
Source DB: PubMed Journal: Biochim Biophys Acta Mol Basis Dis ISSN： 0925-4439 Impact factor: 5.187