2. Academic Validation
  3. Impaired histone inheritance promotes tumor progression

Impaired histone inheritance promotes tumor progression

  • Nat Commun. 2023 Jun 10;14(1):3429. doi: 10.1038/s41467-023-39185-y.
Congcong Tian # 1,  Jiaqi Zhou # 1,  Xinran Li # 1,  Yuan Gao 2,  Qing Wen 1,  Xing Kang 1,  Nan Wang 1,  Yuan Yao 1,  Jiuhang Jiang 1 3,  Guibing Song 1 4,  Tianjun Zhang 1 5,  Suili Hu 1 3,  JingYi Liao 1,  Chuanhe Yu 6,  Zhiquan Wang 7,  Xiangyu Liu 8,  Xinhai Pei 9,  Kuiming Chan 10 11,  Zichuan Liu 12,  Haiyun Gan 13
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic Genomics, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055, Shenzhen, China.
  • 2 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA.
  • 3 College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, 510642, Guangzhou, Guangdong, China.
  • 4 College of Animal Science and Technology, Northwest A&F University, 712100, Shaanxi, Angling, China.
  • 5 Department of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, SA, 5005, Australia.
  • 6 Hormel Institute, University of Minnesota, Austin, MN, 55912, USA.
  • 7 Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
  • 8 Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, International Cancer Center, Marshall Laboratory of Biomedical Engineering, Shenzhen University Health Science Center, 518060, Shenzhen, China.
  • 9 Department of Anatomy and Histology, Shenzhen University Health Science Center, 518060, Shenzhen, China.
  • 10 Department of Biomedical Sciences, City University of Hong Kong, Hong Kong Special Administration Region, China.
  • 11 Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, 518172, Shenzhen, China.
  • 12 School of Pharmaceutical Science and Technology, Tianjin University and Health-Biotech United Group Joint Laboratory of Innovative Drug Development and Translational Medicine, Tianjin University, 300072, Tianjin, China.
  • 13 CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic Genomics, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055, Shenzhen, China. hy.gan@siat.ac.cn.
  • # Contributed equally.
PMID: 37301892 DOI: 10.1038/s41467-023-39185-y
Abstract

Faithful inheritance of parental histones is essential to maintain epigenetic information and cellular identity during cell division. Parental histones are evenly deposited onto the replicating DNA of sister chromatids in a process dependent on the MCM2 subunit of DNA helicase. However, the impact of aberrant parental histone partition on human disease such as Cancer is largely unknown. In this study, we construct a model of impaired histone inheritance by introducing MCM2-2A mutation (defective in parental histone binding) in MCF-7 breast Cancer cells. The resulting impaired histone inheritance reprograms the histone modification landscapes of progeny cells, especially the repressive histone MARK H3K27me3. Lower H3K27me3 levels derepress the expression of genes associated with development, cell proliferation, and epithelial to mesenchymal transition. These epigenetic changes confer fitness advantages to some newly emerged subclones and consequently promote tumor growth and metastasis after orthotopic implantation. In summary, our results indicate that impaired inheritance of parental histones can drive tumor progression.

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