Review
Pharmacology & Pharmacy
Chang-Yun Li, Yan-Jun Liu, Fan Tao, Ru-Yi Chen, Jin-Jin Shi, Jian-Fei Lu, Guan -Jun Yang, Jiong Chen
Summary: This article discusses the important role of lysine-specific demethylase 7A (KDM7A) in biological regulation and disease development, as well as its structure, function, and potential drug treatments. KDM7A is not only crucial for normal development but also associated with various diseases.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yifan Wang, Qin Hong, Yueyue Xia, Zhao Zhang, Bo Wen
Summary: The lysine demethylase KDM7A has important functions in neuronal cells, regulating the expression of immediate early genes (IEGs) and affecting neuron activity, emotion, and memory. These findings provide new insights into the epigenetic mechanisms of neurological disorders.
Article
Cell Biology
Ziyu Zhang, Baoyu Chen, Yuwen Zhu, Tianyi Zhang, Yibiao Yuan, Xiaoling Zhang, Yong Xu
Summary: TGF-beta regulates the transcription of the prometastatic small GTPase RHOJ by activating MKL1 and recruiting the H3K9/H3K27 dual demethylase KDM7A. KDM7A can be used to predict prognosis in breast cancer patients and its knockdown attenuates migration, invasion, growth, and metastasis of breast cancer cells. KDM7A is a direct transcriptional target of TGF-beta signaling, and small-molecule inhibitors of KDM7A may provide therapeutic solutions for malignant breast cancers.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ji-Hyun Kim, Arukumar Nagappan, Dae Young Jung, Nanjoo Suh, Myeong Ho Jung
Summary: The study shows that histone demethylase KDM7A promotes hepatic steatosis by upregulating DGAT2 expression, leading to nonalcoholic fatty liver disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Anatomy & Morphology
Davide Martini, Matteo Digregorio, Ilaria Anna Pia Voto, Giuseppe Morabito, Andrea Degl'Innocenti, Guido Giudetti, Martina Giannaccini, Massimiliano Andreazzoli
Summary: KDM7A is an important histone lysine demethylase that plays a critical role in embryonic development and pathological conditions. This study found that KDM7A is dynamically expressed throughout embryonic development and its overexpression affects the distribution of neuronal subtypes in retinal development.
DEVELOPMENTAL DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Cheng Zeng, Jiwei Chen, Emmalee W. Cooke, Arijita Subuddhi, Eliana T. Roodman, Fei Xavier Chen, Kaixiang Cao
Summary: This study reveals the catalytic-independent role of LSD1 in regulating gene expression and cellular differentiation, demonstrating that the loss of LSD1 protein globally de-represses enhancers and impairs cell fate transition. The researchers found that the increase of H3K27ac catalyzed by P300/CBP, rather than the loss of CoREST complex components from chromatin, contributes to the transcription de-repression of LSD1 targets and differentiation defects caused by LSD1 loss.
NATURE COMMUNICATIONS
(2023)
Review
Plant Sciences
Hongmiao Hu, Jiamu Du
Summary: This review focuses on the central role of histone methylation in regulating chromatin state and gene expression in Arabidopsis. It summarizes the current understanding of the dynamic regulation of histone methylation, with a particular emphasis on the histone methyltransferases and demethylases involved.
CURRENT OPINION IN PLANT BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shusei Mori, Satoyo Oya, Mayumi Takahashi, Kazuya Takashima, Soichi Inagaki, Tetsuji Kakutani
Summary: Based on studies of the plant genome, it has been found that the demethylation of H3K4me2 plays a negative regulatory role in transcriptionally active genes. A previous study identified a key demethylase LDL3, which interacts with RNA polymerase II and RNA transcription elongation factors to demethylate H3K4me2. These findings suggest that H3K4me2 demethylation serves as a chromatin record of transcriptional activity in plants, ensuring robust gene control.
Article
Multidisciplinary Sciences
Bi Shi, Wei Li, Yansu Song, Zhenjia Wang, Rui Ju, Aleksandra Ulman, Jing Hu, Francesco Palomba, Yanfang Zhao, John Philip Le, William Jarrard, David Dimoff, Michelle A. Digman, Enrico Gratton, Chongzhi Zang, Hao Jiang
Summary: UTX, a histone H3K27 demethylase, is an important tumour suppressor frequently mutated in human cancers. This study reveals that phase separation of UTX underlies its chromatin-regulatory activity in tumour suppression. UTX recruits histone methyltransferase MLL4 to condensates and enriches MLL4's activity, demonstrating the crucial role of liquid condensates in the tumour-suppressive activity of a chromatin regulator.
Review
Chemistry, Medicinal
Yihui Song, Huiqing Zhang, Xiaoke Yang, Yuting Shi, Bin Yu
Summary: Lysine-specific demethylase 1 (LSD1/KDM1A) has emerged as a promising epigenetic target for disease treatment. This review provides an update on LSD1 inhibitors, including natural products, synthetic compounds, and cyclic peptides reported in 2021. The design strategies, structure-activity relationships, binding model analysis, and modes of action are discussed. Highlights include the repurposing of FDA-approved drugs as reversible LSD1 inhibitors, the identification of clinical candidates for neuro-developmental disorders, and the enhanced anti-cancer effects of dual inhibitors targeting both LSD1 and HDAC6 or tubulin.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Cell Biology
Delia Cicciarello, Laurent Schaeffer, Isabella Scionti
Summary: Adult skeletal muscle is composed of multinucleated muscle fibers and has the ability to regenerate. The fate of muscle stem cells is determined by intrinsic and extrinsic factors as well as the expression of specific gene subsets. Histone demethylases play a crucial role in the fate choice of muscle stem cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Miaojuan Fan, Tongtong Pan, Wei Jin, Jian Sun, Shujun Zhang, Yali Du, Xinwei Chen, Qiong Chen, Wenxin Xu, Siew Woh Choo, Guanghui Zhu, Yongping Chen, Jie Zhou
Summary: The study revealed elevated expression of FGF4 in GDM patients, with rFGF4 treatment effectively normalizing adverse metabolic phenotypes and reducing neural tube defects in GDM mice. The findings suggest FGF4 as a potential diagnostic factor and therapeutic target for GDM.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Chemistry, Medicinal
Dong-Jun Fu, Jun Li, Bin Yu
Summary: This review highlights the research progress of LSD1 inhibitors, categorizing them into natural and synthetic compounds. The potential of these inhibitors in cancer treatment, as well as related design strategies, are discussed.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Yajing Meng, Tianzhe Zhang, Ran Zheng, Song Ding, Jie Yang, Ran Liu, Yingan Jiang, Wei Jiang
Summary: The study demonstrated the crucial role of KDM6B in early neuroectoderm commitment from human embryonic stem cells, showing that KDM6B knockout significantly increased neuroectoderm induction efficiency. Furthermore, KDM6 was found to regulate early neural induction through the modulation of WNT genes. Additionally, the inhibitor of KDM6, GSK-J1, enhanced neuroectoderm differentiation from both embryonic stem cells and induced pluripotent stem cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Ling Tian, Monique Chavez, Gue Su Chang, Nichole M. Helton, Casey D. S. Katerndahl, Christopher A. Miller, Lukas D. Wartman
Summary: The study found that female Kdm6a knockout mice exhibit features resembling myelodysplastic syndrome as they age, indicating that Kdm6a plays an important role in normal hematopoiesis and its inactivation may contribute to the pathogenesis of AML.
Article
Cell & Tissue Engineering
Ting Zhang, Wei Ke, Xuan Zhou, Yun Qian, Su Feng, Ran Wang, Guizhong Cui, Ran Tao, Wenke Guo, Yanhong Duan, Xiaobing Zhang, Xiaohua Cao, Yousheng Shu, Chunmei Yue, Naihe Jing
Article
Cell & Tissue Engineering
Jianrui Ma, Chengyang Huang
TISSUE ENGINEERING PART B-REVIEWS
(2020)
Article
Cell Biology
Ran Tao, Rui Lu, Junfeng Wang, Shujun Zeng, Ting Zhang, Wenke Guo, Xiaobing Zhang, Qi Cheng, Chunmei Yue, Yizheng Wang, Naihe Jing
JOURNAL OF MOLECULAR CELL BIOLOGY
(2020)
Article
Cell Biology
Fei Sun, Terrence Sun, Michael Kronenberg, Xianglong Tan, Chengyang Huang, Michael F. Carey
Summary: The degradation of TAF12 and MED4 in murine embryonic stem cells revealed their different roles in P-E communication, with neither directly controlling P-E looping. Degradation of TAF12 led to a significant decrease in gene expression, while degradation of MED4 consistently led to a twofold loss in gene expression.
GENES & DEVELOPMENT
(2021)
Article
Cell Biology
Jianneng Li, Michael Berk, Mohammad Alyamani, Navin Sabharwal, Christopher Goins, Joseph Alvarado, Mehdi Baratchian, Ziqi Zhu, Shaun Stauffer, Eric A. Klein, Nima Sharifi
Summary: The study identified that up-regulation of H6PD protein in prostate cancer tissues of men treated with enzalutamide is associated with tumor resistance. Silencing H6PD blocks NADPH generation and reverses resistance. Pharmacologic intervention of H6PD normalizes tumor metabolism and increases sensitivity to enzalutamide.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Ophthalmology
Xin-Yue Zhu, Yu Hong Chen, Ting Zhang, Su-Jun Liu, Xin-Yue Bai, Xian-Yu Huang, Mei Jiang, Xiao-Dong Sun
Summary: In this study, it was found that truncated recombinant human vitronectin (VTN-N) is a more suitable coating substrate for cultivating hES-RPE cells. Cells cultured on VTN-N substrate showed enhanced phagocytic ability and faster maturation compared to cells cultured on LN-521.
INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
(2021)
Article
Ophthalmology
Yuhong Chen, Xinyue Zhu, Fuxiang Ye, Hong Wang, Xiaoling Wan, Ting Zhang, Yuwei Wang, Yimin Wang, Xiaohuan Zhao, Xinyue Bai, Yushu Xiao, Xiaodong Sun
Summary: This study established a novel CNV mouse model by subretinally injecting MDA-modified POS, which simulates the AMD pathological process. Results showed that MDA-modified POS induced CNV and RPE atrophy, increased VEGF expression, disrupted RPE cell junctions, and caused autophagy-lysosomal impairment in RPE cells.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Feng Yue, Su Feng, Chunlin Lu, Ting Zhang, Guoxian Tao, Jing Liu, Chunmei Yue, Naihe Jing
Summary: The injection of synthetic A beta oligomers into the brains of cynomolgus monkeys rapidly led to the formation of A beta plaques and neurofibrillary tangles, triggering neuroinflammation and degenerative changes similar to those seen in Alzheimer's disease patients. This study suggests the development of a promising animal model for human Alzheimer's disease in non-human primates.
Article
Oncology
Liang Qin, Yoon-Mi Chung, Michael Berk, Bryan Naelitz, Ziqi Zhu, Eric Klein, Abhishek A. Chakraborty, Nima Sharifi
Summary: This study reveals that hypoxia followed by reoxygenation in prostate cancer increases the rate-limiting enzyme and cofactors for androgen synthesis, leading to resistance to androgen deprivation therapy. The study also identifies HIF2α as a potential therapeutic target for prostate cancer.
Article
Biochemistry & Molecular Biology
Chengyang Huang, Wanqiong Huang, Pengchao Ji, Fuling Song, Tao Liu, Meiyang Li, Hongzhi Guo, Yongliang Huang, Cuicui Yu, Chuanxian Wang, Wenxiu Ni
Summary: The synthesized osmium(VI) nitrido complex has shown inhibitory effects on cervical, ovarian, and breast cancer cell lines, and modulates protein expression in HepG2 cells affecting mitochondrial function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Di Cui, Jianneng Li, Ziqi Zhu, Michael Berk, Aimalie Hardaway, Jeffrey McManus, Yoon-Mi Chung, Mohammad Alyamani, Shelley Valle, Ritika Tiwari, Bangmin Han, Maryam Goudarzi, Belinda Willard, Nima Sharifi
Summary: After androgen deprivation, prostate cancer frequently becomes castration resistant (CRPC), involving intratumoral androgen production. Cancer-associated fibroblasts (CAFs) increase 3 beta HSD1 expression and induce androgen synthesis, leading to CRPC.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Medicine, Research & Experimental
Xiuxiu Li, Michael Berk, Christopher Goins, Mohammad Alyamani, Yoon-Mi Chung, Chenyao Wang, Monaben Patel, Nityam Rathi, Ziqi Zhu, Belinda Willard, Shaun Stauffer, Eric Klein, Nima Sharifi
Summary: Prostate cancer depends on androgens and the androgen receptor (AR). Resistance to medical castration leads to castration-resistant prostate cancer (CRPC) driven by the reactivation of the androgen-AR axis. 3 beta HSD1 plays a critical role in stimulating CRPC and is also essential for breast cancer in postmenopausal women. The phosphorylation of tyrosine 344 (Y344) is required for 3 beta HSD1 activity and the synthesis of androgens and estrogens.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biology
Xianfa Yang, Yingying Chen, Lu Song, Ting Zhang, Naihe Jing
Summary: The regionalized distribution of genes is crucial in spatial pattern formation during development. In situ hybridization remains a widely used method for screening and identifying gene distribution in tissues and embryos, but maintaining high-quality signals can be challenging, especially for small tissues like early post-implantation mouse embryos. This protocol outlines a detailed RNA in situ hybridization method for whole-mount early post-implantation mouse embryos and other small tissue samples, utilizing DIG-labeled riboprobes and color development substrates for visualization.
Article
Biochemical Research Methods
Ting Zhang, Ran Tao, Chunmei Yue, Naihe Jing
Summary: This reliable protocol allows for the generation of integration-free human iNPCs from a small volume of immobilized adult peripheral blood, which can efficiently differentiate into mature neurons with the potential to replace damaged neurons.
Article
Oncology
Xiaomei Gao, Charles Dai, Shengsong Huang, Jingjie Tang, Guoyuan Chen, Jianneng Li, Ziqi Zhu, Xuyou Zhu, Shuirong Zhou, Yuanyuan Gao, Zemin Hou, Zijun Fang, Chengdang Xu, Jianyang Wang, Denglong Wu, Nima Sharifi, Zhenfei Li
CLINICAL CANCER RESEARCH
(2019)
