Article
Cell Biology
Chang Sun, Yuan Qi, Natalie Fowlkes, Nina Lazic, Xiaoping Su, Guillermina Lozano, Amanda R. Wasylishen
Summary: Daxx functions as a histone chaperone for the histone H3 variant H3.3 and is essential for embryonic development. It interacts with Atrx to deposit H3.3 into heterochromatin, and this interaction is dispensable for viability. However, the interaction between Daxx and H3.3 is essential for postnatal viability and is important for silencing endogenous retroviruses and maintaining proper immune cell composition.
CELL DEATH & DISEASE
(2023)
Review
Endocrinology & Metabolism
Fei Wang, Xiaowu Xu, Zeng Ye, Yi Qin, Xianjun Yu, Shunrong Ji
Summary: This study is the first rigorous pooled analysis assessing ATRX/DAXX mutations as prognostic biomarkers in PanNETs. The results indicate that patients with altered ATRX/DAXX genes have poor DFS, while altered ATRX/DAXX genes in metastatic patients show a trend towards improved overall survival.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Genetics & Heredity
Sarah F. Clatterbuck F. Soper, Paul S. Meltzer
Summary: Proliferating cells need a telomere maintenance mechanism for genomic stability. In some tumors, telomeres are maintained through an alternate lengthening mechanism called ALT, which is associated with mutations in the ATRX/DAXX/H3.3 histone chaperone complex. This complex is responsible for histone deposition and has roles in replication and DNA repair. This review will discuss the protective role of ATRX/DAXX in the genome and how its loss facilitates ALT.
Article
Multidisciplinary Sciences
Sara Priego Moreno, Javier Miralles Fuste, Melanie Kaiser, Julia Su Zhou Li, Joe Nassour, Candy Haggblom, Eros Lazzerini Denchi, Jan Karlseder
Summary: The appropriate regulation of telomere length homeostasis is crucial for genome integrity. The telomere-binding protein TZAP has been suggested to regulate telomere length through telomere trimming, but the molecular mechanisms are not understood. In this study, we found that TZAP can efficiently bind to telomeres in the absence of ATRX/DAXX and induce telomere dysfunction and ALT-like activity, resulting in the generation of t-circles and c-circles in a BTR-dependent manner.
Article
Biochemistry & Molecular Biology
Ingie Elchennawi, Philippe Carpentier, Christelle Caux, Marine Ponge, Sandrine Ollagnier de Choudens
Summary: Iron-sulfur (Fe-S) clusters are essential for cellular pathways and require proteins to mobilize sulfur and iron for their assembly. The SUF system in Mycobacterium tuberculosis is the primary Fe-S biogenesis system and a potential target for fighting tuberculosis. In this study, two proteins of the Mtb SUF system, Rv1464(sufS) and Rv1465(sufU), were characterized and their interaction and activities in Fe-S biogenesis were investigated.
Article
Genetics & Heredity
Radwa Sharaf, Meagan Montesion, Julia F. Hopkins, Jiarong Song, Garrett M. Frampton, Lee A. Albacker
Summary: This study highlights the importance of RAD21 and HGF in telomere lengthening, supporting unlimited replication in tumors. These findings open avenues for work aimed at targeting this crucial pathway in tumorigenesis.
Review
Oncology
Claudio Luchini, Rita T. Lawlor, Samantha Bersani, Caterina Vicentini, Gaetano Paolino, Paola Mattiolo, Antonio Pea, Sara Cingarlini, Michele Milella, Aldo Scarpa
Summary: In pancreatic neuroendocrine tumors (PanNET), ALT is strongly correlated with the mutational status of two chromatin remodeling genes, DAXX and ATRX. ALT emerged as a reliable indicator of worse prognosis for PanNET, aiding in clinical stratification and identification of high-risk patients, and supporting the pancreatic origin of neuroendocrine tumors for improving diagnostic workflow in patients with neuroendocrine metastasis from unknown primary.
CURRENT ONCOLOGY REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Irina Bogolyubova, Dmitry Bogolyubov
Summary: DAXX is a multifunctional protein involved in various cellular processes, interacting with transcription factors and chromatin-remodeling proteins in the nucleus. Its specific function in mammalian early development as a chaperone of H3.3 supports proper development, impacting recruitment of ATRX and transcription of tandem repeats. Loss of DAXX results in decreased viability of early embryos.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Giuseppe Lamberti, Natalie Prinzi, Alberto Bongiovanni, Mariangela Torniai, Elisa Andrini, Dario de Biase, Deborah Malvi, Mirta Mosca, Rossana Berardi, Toni Ibrahim, Sara Pusceddu, Davide Campana
Summary: This study investigated the molecular features and treatment response of grade 3 gastro-entero-pancreatic neuroendocrine tumors (G3 GEP-NET). The findings showed that FOLFOX/XELOX chemotherapy is effective as a first-line treatment for G3 GEP-NET. The mutational landscape of G3 NET is more similar to well-differentiated NETs.
Article
Cell Biology
Chang Sun, Jeannelyn S. Estrella, Elizabeth M. Whitley, Gilda P. Chau, Guillermina Lozano, Amanda R. Wasylishen
Summary: The study reveals that Daxx and Atrx are not effective tumor suppressors in the endocrine pancreas of mice, and emphasizes the importance of the genomic context for tumorigenesis.
DISEASE MODELS & MECHANISMS
(2022)
Article
Biochemistry & Molecular Biology
Felix J. Metzner, Elisabeth Huber, Karl-Peter Hopfner, Katja Lammens
Summary: The Schlafen family, including SLFN5, plays important roles in cell cycle regulation, DNA repair, etc. The structure of SLFN5 differs from ATPase and can bind both tRNA and DNA, possibly involved in transcriptional regulation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Pathology
Jacqueline A. Brosnan-Cashman, Christine M. Davis, Bill H. Diplas, Alan K. Meeker, Fausto J. Rodriguez, Christopher M. Heaphy
Summary: The study found that a subset of giant cell GBM utilizes the ALT telomere maintenance mechanism, and in addition to ATRX loss, tumors with SMARCAL1 alterations are prevalent in giant cell GBM.
Article
Cell Biology
Doreen Maria Gisder, Oliver Overheu, Julia Keller, Stefanie Nopel-Dunnebacke, Waldemar Uhl, Anke Reinacher-Schick, Andrea Tannapfel, Iris Tischoff
Summary: The loss of DAXX and ATRX immunoreactivity is associated with the aggressiveness and prognosis of PanNETs. The loss of DAXX is a stronger indicator, while the loss of ATRX is weaker.
Article
Biochemistry & Molecular Biology
Pengjiao Hou, Wei Hao, Bo Qin, Mengyun Li, Rong Zhao, Sheng Cui
Summary: Schlafen11 is a well-studied protein that plays important roles in cancer therapy and virus-host interactions. The crystal structure and biochemical characteristics of the N-terminal domain (NTD) of Schlafen11 were determined, revealing its potent RNase activity towards type I and II tRNAs and rRNAs. These findings enhance our understanding of the Schlafen family.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Massimo Carraro, Ivo A. Hendriks, Colin M. Hammond, Victor Solis-Mezarino, Moritz Volker-Albert, Jonas D. Elsborg, Melanie B. Weisser, Christos Spanos, Guillermo Montoya, Juri Rappsilber, Axel Imhof, Michael L. Nielsen, Anja Groth
Summary: This study expands the role of ASF1 in histone dynamics by uncovering the interaction between ASF1 and SPT2 subunits. It also reveals the unique functionality of DAXX in the histone chaperone network, recruiting histone methyltransferases to catalyze H3K9me3 on newly synthesized histone H3.3-H4 prior to deposition onto DNA. Thus, DAXX provides a molecular mechanism for de novo H3K9me3 deposition and heterochromatin assembly.
Article
Cell Biology
Min Zhang, Shumin Yang, Raman Nelakanti, Wentao Zhao, Gaochao Liu, Zheng Li, Xiaohui Liu, Tao Wu, Andrew Xiao, Haitao Li
Letter
Cell Biology
Yihui Zheng, Xingrun Zhang, Haitao Li
Article
Biochemistry & Molecular Biology
Fan Zhao, Yunan Liu, Xiaonan Su, Ji-Eun Lee, Yutong Song, Daliang Wang, Kai Ge, Juntao Gao, Michael Q. Zhang, Haitao Li
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Xiangle Ren, Yang Zhou, Zhaoyu Xue, Ning Hao, Yuanyuan Li, Xiaohuan Guo, Daliang Wang, Xiaobing Shi, Haitao Li
Summary: This study identified the first readers for histone Kbz and revealed the molecular mechanisms underlying Kbz recognition, paving the way for further functional dissections of histone benzoylation.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Huitao Fan, Yiran Guo, Yi-Hsuan Tsai, Aaron J. Storey, Arum Kim, Weida Gong, Ricky D. Edmondson, Samuel G. Mackintosh, Haitao Li, Stephanie D. Byrum, Alan J. Tackett, Ling Cai, Gang Greg Wang
Summary: Trimethylation of histone H3 lysine 27 (H3K27me3) plays a crucial role in gene silencing and imprinting, (epi)genome organization, and organismal development. This study reveals that the Bromo Adjacent Homology (BAH) domain within BAH domain-containing protein 1 (BAHD1) is essential for the targeting of BAHD1 to chromatin and optimal repression of H3K27me3-demarcated genes in mammalian cells. Disruption of the direct interaction between BAHD1(BAH) and H3K27me3 leads to chromatin remodeling and increased histone acetylation at Polycomb gene targets, affecting embryonic development.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Lei Yang, Rong-Chang Li, Bin Xiang, Yi-Chen Li, Li-Peng Wang, Yun-Bo Guo, Jing-Hui Liang, Xiao-Ting Wang, Tingting Hou, Xin Xing, Zeng-Quan Zhou, Haihong Ye, Ren-Qing Feng, Edward G. Lakatta, Zhen Chai, Shi-Qiang Wang
Summary: The contraction of heart cells is regulated by the signaling interaction between LCCs and RyRs, which is influenced by the nanodistance between JPH2 in the SR and CAV3 in the TT. Our study revealed that SRF and myocardin concurrently regulate the expression of JPH2 and CAV3, leading to enhanced efficiency of LCC-RyR signaling and compensation for LCC down-regulation during hibernation, maintaining heart power and avoiding calcium overload.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemical Research Methods
Tingzhong Tian, Shuya Li, Peng Lang, Dan Zhao, Jianyang Zeng
Summary: The study presents a deep learning based approach called RiboMIMO for modeling ribosome density distributions of full-length mRNA coding regions. By considering correlations in translation efficiency among neighboring and remote codons, RiboMIMO outperforms existing computational approaches and accurately predicts ribosome density distributions. This study's findings suggest that remote codons may have an impact on translation elongation rates, providing insights into potential regulatory mechanisms of protein synthesis.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Letter
Cell Biology
Zimo Yang, Yonghui Sun, Zhihao Ni, Celi Yang, Yan Tong, Yujie Liu, Haitao Li, Yu Rao
Article
Biochemistry & Molecular Biology
Shuangping Zheng, Yucong Bi, Haining Chen, Bo Gong, Shunji Jia, Haitao Li
Summary: The protein PHF14 plays a critical role in recognizing unmodified histone H3(1-34) through a bipartite recognition mechanism. PHF14 utilizes distinct surfaces to engage different segments of H3(1-34) and is sensitive to specific modifications on H3 residues. This study provides insights into the repressive function of PHF14 and its regulation by histone modifications.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Yipin Lei, Shuya Li, Ziyi Liu, Fangping Wan, Tingzhong Tian, Shao Li, Dan Zhao, Jianyang Zeng
Summary: The authors proposed a deep learning framework CAMP for predicting peptide-protein interactions and identifying important binding residues. Comprehensive evaluation showed that CAMP outperformed other methods in predicting peptide-protein interactions. CAMP serves as a significant tool in facilitating peptide drug discovery.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Yuhong Yang, Yuanyuan Xu, Yuan Yue, Heng Wang, Yumeng Cui, Miaomiao Pan, Xi Zhang, Lin Zhang, Haitao Li, Min Xu, Yefeng Tang, Shawn Chen
Summary: Indolmycin (IND) is a microbial natural product that selectively inhibits bacterial tryptophanyl-tRNA synthetase (TrpRS). IND shows promising antibacterial activity against Mycobacterium tuberculosis (Mtb), especially the 4''-methylated compound Y-13. The cocrystal structure of Mtb TrpRS complexed with IND and ATP reveals that IND can affect the activity of TrpRS and has synergistic effects with other antibacterial agents, potentially leading to the development of new antibiotics.
ACS CHEMICAL BIOLOGY
(2022)
Article
Cell Biology
Yi Shi, Yuan Liao, Qianlong Liu, Zhihao Ni, Zhenzhen Zhang, Minglei Shi, Pilong Li, Haitao Li, Yu Rao
Summary: Biomolecular condensates play important roles in biological processes, and PROTAC is a new technology that can specifically degrade target proteins using small molecules. This study used a BRD4-targeting PROTAC molecule to regulate the super-enhancer condensate and found that it can significantly reduce BRD4 condensates. It also established a method to track BRD4 condensates using PROTAC and cellular imaging.
Article
Computer Science, Artificial Intelligence
Xingang Peng, Yipin Lei, Peiyuan Feng, Lemei Jia, Jianzhu Ma, Dan Zhao, Jianyang Zeng
Summary: Studying the interactions between T-cell receptors (TCRs) and epitopes is crucial for immunotherapy and antigen discovery. Researchers developed a new deep-learning-based model to predict TCR-epitope interactions, providing valuable insights into binding mechanisms.
NATURE MACHINE INTELLIGENCE
(2023)
Article
Computer Science, Interdisciplinary Applications
Hantao Shu, Jingtian Zhou, Qiuyu Lian, Han Li, Dan Zhao, Jianyang Zeng, Jianzhu Ma
Summary: DeepSEM is a deep generative model that can jointly infer gene regulatory networks (GRNs) and biologically meaningful representation of single-cell RNA sequencing (scRNA-seq) data. By developing a neural network version of the structural equation model (SEM), DeepSEM outperforms existing methods on various single-cell computational tasks and the predicted gene regulations can be validated by epigenetic data.
NATURE COMPUTATIONAL SCIENCE
(2021)
Article
Computer Science, Artificial Intelligence
Lixiang Hong, Jinjian Lin, Shuya Li, Fangping Wan, Hui Yang, Tao Jiang, Dan Zhao, Jianyang Zeng
NATURE MACHINE INTELLIGENCE
(2020)
