Year
Month
(Peer-Reviewed) Incorporation of a histone mutant with H3K56 site substitution perturbs the replication machinery in mouse embryonic stem cells
Xuan Kang ¹, Xiaomei Yang ¹, Xiaobo Guo ¹, Yabin Li ¹, Chenxin Yang ¹, Huimin Wei ¹ ², Jianfeng Chang 常建锋 ¹
¹ Research Center for Translational Medicine, East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
中国 上海 同济大学生命科学与技术学院东方医院转化医学研究中心
² Tsingdao Advanced Research Institute, Tongji University, Qingdao 266071, China
同济大学青岛高等研究院
Abstract

Sense mutations in several conserved modifiable sites of histone H3 have been found to be strongly correlated with multiple tissue-specific clinical cancers. These clinical site mutants acquire a distinctively new epigenetic role and mediate cancer evolution. In this study, we mimicked histone H3 at the 56th lysine (H3K56) mutant incorporation in mouse embryonic stem cells (mESCs) by lentivirus-mediated ectopic expression and analyzed the effects on replication and epigenetic regulation.

The data show that two types of H3K56 mutants, namely H3 lysine 56-to-methionine (H3K56M) and H3 lysine 56-to-alanine (H3K56A), promote replication by recruiting more minichromosome maintenance complex component 3 and checkpoint kinase 1 onto chromatin compared with wild-type histone H3 and other site substitution mutants. Under this condition, the frequency of genomic copy number gain in H3K56M and H3K56A cells globally increases, especially in the Mycl1 region, a known molecular marker frequently occurring in multiple malignant cancers.

Additionally, we found the disruption of H3K56 acetylation distribution in the copy-gain regions, which indicates a probable epigenetic mechanism of H3K56M and H3K56A. We then identified that H3K56M and H3K56A can trigger a potential adaptation to transcription; genes involved in the mitogen-activated protein kinase pathway are partially upregulated, whereas genes associated with intrinsic apoptotic function show obvious downregulation. The final outcome of ectopic H3K56M and H3K56A incorporation in mESCs is an enhanced ability to form carcinomas.

This work indicates that H3K56 site conservation and proper modification play important roles in harmonizing the function of the replication machinery in mESCs.
Incorporation of a histone mutant with H3K56 site substitution perturbs the replication machinery in mouse embryonic stem cells_1
Incorporation of a histone mutant with H3K56 site substitution perturbs the replication machinery in mouse embryonic stem cells_2
Incorporation of a histone mutant with H3K56 site substitution perturbs the replication machinery in mouse embryonic stem cells_3
Incorporation of a histone mutant with H3K56 site substitution perturbs the replication machinery in mouse embryonic stem cells_4
  • Ultrahigh performance passive radiative cooling by hybrid polar dielectric metasurface thermal emitters
  • Yinan Zhang, Yinggang Chen, Tong Wang, Qian Zhu, Min Gu
  • Opto-Electronic Advances
  • 2024-03-12
  • Simultaneously realizing thermal and electromagnetic cloaking by multi-physical null medium
  • Yichao Liu, Xiaomin Ma, Kun Chao, Fei Sun, Zihao Chen, Jinyuan Shan, Hanchuan Chen, Gang Zhao, Shaojie Chen
  • Opto-Electronic Science
  • 2024-02-29
  • Generation of lossy mode resonances (LMR) using perovskite nanofilms
  • Dayron Armas, Ignacio R. Matias, M. Carmen Lopez-Gonzalez, Carlos Ruiz Zamarreño, Pablo Zubiate, Ignacio del Villar, Beatriz Romero
  • Opto-Electronic Advances
  • 2024-02-26
  • Acousto-optic scanning multi-photon lithography with high printing rate
  • Minghui Hong
  • Opto-Electronic Advances
  • 2024-02-26
  • Tailoring electron vortex beams with customizable intensity patterns by electron diffraction holography
  • Pengcheng Huo, Ruixuan Yu, Mingze Liu, Hui Zhang, Yan-qing Lu, Ting Xu
  • Opto-Electronic Advances
  • 2024-02-26
  • Miniature tunable Airy beam optical meta-device
  • Jing Cheng Zhang, Mu Ku Chen, Yubin Fan, Qinmiao Chen, Shufan Chen, Jin Yao, Xiaoyuan Liu, Shumin Xiao, Din Ping Tsai
  • Opto-Electronic Advances
  • 2024-02-26
  • Data-driven polarimetric imaging: a review
  • Kui Yang, Fei Liu, Shiyang Liang, Meng Xiang, Pingli Han, Jinpeng Liu, Xue Dong, Yi Wei, Bingjian Wang, Koichi Shimizu, Xiaopeng Shao
  • Opto-Electronic Science
  • 2024-02-24
  • Towards the performance limit of catenary meta-optics via field-driven optimization
  • Siran Chen, Yingli Ha, Fei Zhang, Mingbo Pu, Hanlin Bao, Mingfeng Xu, Yinghui Guo, Yue Shen, Xiaoliang Ma, Xiong Li, Xiangang Luo
  • Opto-Electronic Advances
  • 2024-01-31
  • Broadband high-efficiency dielectric metalenses based on quasi-continuous nanostrips
  • Xiaohu Zhang, Qinmiao Chen, Dongliang Tang, Kaifeng Liu, Haimo Zhang, Lintong Shi, Mengyao He, Yongcai Guo, Shumin Xiao
  • Opto-Electronic Advances
  • 2024-01-31
  • Robust measurement of orbital angular momentum of a partially coherent vortex beam under amplitude and phase perturbations
  • Zhao Zhang, Gaoyuan Li, Yonglei Liu, Haiyun Wang, Bernhard J. Hoenders, Chunhao Liang, Yangjian Cai, Jun Zeng
  • Opto-Electronic Science
  • 2024-01-31
  • Deblurring, artifact-free optical coherence tomography with deconvolution-random phase modulation
  • Xin Ge, Si Chen, Kan Lin, Guangming Ni, En Bo, Lulu Wang, Linbo Liu
  • Opto-Electronic Science
  • 2024-01-31
  • Dynamic interactive bitwise meta-holography with ultra-high computational and display frame rates
  • Yuncheng Liu, Ke Xu, Xuhao Fan, Xinger Wang, Xuan Yu, Wei Xiong, Hui Gao
  • Opto-Electronic Advances
  • 2024-01-25



  • Broad-band spatial light modulation with dual epsilon-near-zero modes                                Highly sensitive and miniature microfiber-based ultrasound sensor for photoacoustic tomography
    About
    |
    Contact
    |
    Copyright © PubCard