Jun 2021, Volume 12 Issue 6

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    Yuanchao Wang
    Yuliang Feng, Xingguo Liu, Siim Pauklin

    Dedifferentiation of cell identity to a progenitor-like or stem cell-like state with increased cellular plasticity is frequently observed in cancer formation. During this process, a subpopulation of cells in tumours acquires a stem cell-like state partially resembling to naturally occurring pluripotent stem cells that are temporarily present during early embryogenesis. Such characteristics allow these cancer stem cells (CSCs) to give rise to the whole tumour with its entire cellular heterogeneity and thereby support metastases formation while being resistant to current cancer therapeutics. Cancer development and progression are demarcated by transcriptional dysregulation. In this article, we explore the epigenetic mechanisms shaping gene expression during tumorigenesis and cancer stem cell formation, with an emphasis on 3D chromatin architecture. Comparing the pluripotent stem cell state and epigenetic reprogramming to dedifferentiation in cellular transformation provides intriguing insight to chromatin dynamics. We suggest that the 3D chromatin architecture could be used as a target for re-sensitizing cancer stem cells to therapeutics.

    Chuan Chen, Wenqiang Liu, Jiayin Guo, Yuanyuan Liu, Xuelian Liu, Jun Liu, Xiaoyang Dou, Rongrong Le, Yixin Huang, Chong Li, Lingyue Yang, Xiaochen Kou, Yanhong Zhao, You Wu, Jiayu Chen, Hong Wang, Bin Shen, Yawei Gao, Shaorong Gao

    N6-methyladenosine (m6A) on chromosome-associated regulatory RNAs (carRNAs), including repeat RNAs, plays important roles in tuning the chromatin state and transcription, but the intrinsic mechanism remains unclear. Here, we report that YTHDC1 plays indispensable roles in the self-renewal and differentiation potency of mouse embryonic stem cells (ESCs), which highly depends on the m6A-binding ability. Ythdc1 is required for sufficient rRNA synthesis and repression of the 2-cell (2C) transcriptional program in ESCs, which recapitulates the transcriptome regulation by the LINE1 scaffold. Detailed analyses revealed that YTHDC1 recognizes m6A on LINE1 RNAs in the nucleus and regulates the formation of the LINE1-NCL partnership and the chromatin recruitment of KAP1. Moreover, the establishment of H3K9me3 on 2C-related retrotransposons is interrupted in Ythdc1-depleted ESCs and inner cell mass (ICM) cells, which consequently increases the transcriptional activities. Our study reveals a role of m6A in regulating the RNA scaffold, providing a new model for the RNA-chromatin cross-talk.

    Xiaojuan Liang, Cong Tao, Jianfei Pan, Lilan Zhang, Lulu Liu, Ying Zhao, Yiping Fan, Chunwei Cao, Jiali Liu, Jin Zhang, Sin Man Lam, Guanghou Shui, Wanzhu Jin, Wei Li, Jianguo Zhao, Kui Li, Yanfang Wang

    RNF20, an E3 ligase critical for monoubiquitination of histone H2B at lysine 120 (H2Bub), has been implicated in the regulation of various cellar processes; however, its physiological roles in adipocytes remain poorly characterized. Here, we report that the adipocyte-specific knockout of Rnf20 (ASKO) in mice led to progressive fat loss, organomegaly and hyperinsulinemia. Despite signs of hyperinsulinemia, normal insulin sensitivity and improved glucose tolerance were observed in the young and aged CD-fed ASKO mice. In addition, high-fat dietfed ASKO mice developed severe liver steatosis. Moreover, we observed that the ASKO mice were extremely sensitive to a cold environment due to decreased expression levels of brown adipose tissue (BAT) selective genes, including uncoupling protein 1 (Ucp1), and impaired mitochondrial functions. Significantly decreased levels of peroxisome proliferator-activated receptor gamma (Pparγ) were observed in the gonadal white adipose tissues (gWAT) from the ASKO mice, suggesting that Rnf20 regulates adipogenesis, at least in part, through Pparγ. Rosiglitazone-treated ASKO mice exhibited increased fat mass compared to that of the non-treated ASKO mice. Collectively, our results illustrate the critical role of RNF20 in control of white and brown adipose tissue development and physiological function.

    Zhaomeng Cui, Yang Liu, Wei Wan, Yuyan Xu, Yehui Hu, Meng Ding, Xin Dou, Ruina Wang, Hailing Li, Yongmei Meng, Wei Li, Wei Jiang, Zengxia Li, Yiming Li, Minjia Tan, Dengke K. Ma, Yu Ding, Jun O. Liu, Cheng Luo, Biao Yu, Qiqun Tang, Yongjun Dang
    Fangqiao Wei, Xiangyu Sun, Yufeng Gao, Haoyu Dou, Yang Liu, Lili Su, Haofei Luo, Ce Zhu, Qian Zhang, Peiyuan Tong, Wen Ren, Zhe Xun, Ruochun Guo, Yuanlin Guan, Shenghui Li, Yijun Qi, Junjie Qin, Feng Chen, Shuguo Zheng
    Xin Huang, Nazym Bashkenova, Jihong Yang, Dan Li, Jianlong Wang