Nucleotide variation in histone H2BL drives crossalk of histone modification and promotes tumour cell proliferation by upregulating c-Myc

Gene mutations play important roles in tumour development. In this study, we identified a functional histone H2B mutation H2BL-T11C, causing an amino acid variation from Leu to Pro (L3P, H2BL-L3P). Cells overexpressing H2BL-L3P showed stronger proliferation, colony formation, tumourigenic abilities,...

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Bibliographic Details
Published in:Life sciences (1973) 2021-04, Vol.271, p.119127-119127, Article 119127
Main Authors: Zhang, Lei, Zhang, Wei, Sun, Jin, Liu, Kui-nan, Gan, Zhi-xue, Liu, Yu-zhou, Chang, Jian-feng, Yang, Xiao-mei, Sun, Feng
Format: Article
Language:English
Subjects:
Amino acids
Animals
c-Myc
c-Myc protein
Cell cycle
Cell growth
Cell Line, Tumor
Cell proliferation
Cell Proliferation - physiology
Crosstalk
Gene expression
Genetic Variation - genetics
H2BK5ac-H2BK120ubi crosstalk
H2BL/H2BL-L3P
HEK293 Cells
Histone H2B
Histones
Histones - genetics
Histones - metabolism
Humans
Lentivirus
Leucine - genetics
Mice
Mice, Nude
Mutation
Mutation - genetics
Myc protein
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Nucleotides
Nucleotides - genetics
Proline - genetics
Proto-Oncogene Proteins c-myc - biosynthesis
Proto-Oncogene Proteins c-myc - genetics
Single-nucleotide polymorphism
Transcription
Tumors
Tumour cell proliferation
Up-Regulation - physiology
Xenograft Model Antitumor Assays - methods
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Summary:Gene mutations play important roles in tumour development. In this study, we identified a functional histone H2B mutation H2BL-T11C, causing an amino acid variation from Leu to Pro (L3P, H2BL-L3P). Cells overexpressing H2BL-L3P showed stronger proliferation, colony formation, tumourigenic abilities, and a different cell cycle distribution. Meanwhile, the c-Myc expression was elevated as evident by RNA-seq. We further revealed that an H2BK5ac-H2BK120ubi crosstalk which regulates gene transcription. Moreover, EdU staining demonstrated an important role of c-Myc in accelerating cell cycle progression through the G1/S checkpoint, while treatment with 10058-F4, an inhibitor of the c-Myc/MAX interaction, alleviated the abnormal cell proliferation and cell cycle distribution in vitro and partially inhibited tumour growth in vivo. The mutation of amino acid L3P is associated with tumour progression, suggesting patients carrying this SNP may have higher risk of tumour development.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2021.119127