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Biochim Biophys Acta Mol Basis Dis. 2018 Oct;1864(10):3438-3448. doi: 10.1016/j.bbadis.2018.07.033. Epub 2018 Aug 1.

NASP antagonize chromatin accessibility through maintaining histone H3K9me1 in hepatocellular carcinoma.

Author information

1
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, PR China.
2
Translational Center for Stem Cell Research at Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, PR China.
3
School of Medicine, Tsinghua University, Beijing 100084, PR China.
4
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, PR China; School of Forensic Sciences, Xi'an Jiao Tong University Health Science Center, Xi'an, Shaanxi 710061, PR China.
5
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, PR China. Electronic address: yxm411@tongji.edu.cn.
6
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, PR China. Electronic address: jfchang@tongji.edu.cn.

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.

KEYWORDS:

H3K9me1; Liver cancer; NASP; Replication stress; Transcription

PMID:
30076957
DOI:
10.1016/j.bbadis.2018.07.033
[Indexed for MEDLINE]

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