Article
Chemistry, Multidisciplinary
Sumeet K. Singh, Andres Reyna, Xiaowen Xie, Haibin Mao, Meihuan Ji, Ning Zheng, Peter L. Hsu, Champak Chatterjee
Summary: An efficient chemical synthesis method was used to generate site-specifically sumoylated histone H4, resulting in the production of uniformly modified mononucleosomes. These modified mononucleosomes were then used as substrates in biochemical assays with histone H2B-specific ubiquitin ligases Rad6 and Bre1, revealing the strong inhibition of H2B ubiquitylation by SUMO. This novel negative biochemical crosstalk between SUMO and ubiquitin was also confirmed to exist in human cells.
CHEMICAL COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Miyu Sekiguchi, Nobuko Matsushita
Summary: This article provides a comprehensive overview of the role and regulatory mechanism of histone ubiquitination in DNA double-strand break repair.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Biochemistry & Molecular Biology
Jevon A. Cutler, Florian Perner, Scott A. Armstrong
Summary: The research demonstrates that H4K16 acetylation and H2BK120 ubiquitination enhance the methylation of H3K79 by Dot1, suggesting crosstalk between these modifications and providing insight into the role of Dot1 in developmental processes and diseases like MLL1/KMT2A leukemia.
TRENDS IN BIOCHEMICAL SCIENCES
(2021)
Article
Multidisciplinary Sciences
Fei He, Qi Yu, Min Wang, Rongsha Wang, Xuanyunjing Gong, Feng Ge, Xilan Yu, Shanshan Li
Summary: This study reveals the inhibitory effect of H3pT11 on H3K79me3 and uncovers the histone crosstalk regulating autophagy and telomere silencing. It is also discovered that Reb1 recruits the SESAME complex to telomere regions to prevent the invasion of H3K79me3 into heterochromatin, maintaining telomere silencing.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Liying Wang, Zhiliang Xu, Libin Wang, Chao Liu, Huafang Wei, Ruidan Zhang, Yinghong Chen, Lina Wang, Wenwen Liu, Sai Xiao, Wei Li, Wei Li
Summary: The study reveals that RNF20 is crucial for early stage somatic cell reprogramming, with Rnf20 knockout leading to failure in reprogramming at the initial stage. The absence of RNF20 affects the transcription of MET-related genes and early pluripotency genes, ultimately hindering the establishment of a pluripotent gene network.
CELL PROLIFERATION
(2021)
Review
Genetics & Heredity
Lindsey V. Soles, Yongsheng Shi
Summary: APA is a dynamic and highly regulated process that produces multiple mRNA isoforms; mis-regulation of APA has been linked to a variety of diseases. Recent studies have revealed important roles for epigenetic mechanisms in APA regulation.
FRONTIERS IN GENETICS
(2021)
Article
Biology
Matthieu Caron, Loic Gely, Steven Garvis, Annie Adrait, Yohann Coute, Francesca Palladino, Paola Fabrizio
Summary: This study reevaluates the role of H3K4 methylation in the lifespan and fertility of Caenorhabditis elegans, finding that lack of H3K4 methylation leads to shortened lifespan, contrary to previous findings. These results suggest that WT H3K4me2/3 levels are crucial for normal lifespan in C. elegans.
LIFE SCIENCE ALLIANCE
(2021)
Article
Multidisciplinary Sciences
Marco Igor Valencia-Sanchez, Pablo De Ioannes, Miao Wang, David M. Truong, Rachel Lee, Jean-Paul Armache, Jef D. Boeke, Karim-Jean Armache
Summary: This study demonstrates that acetylation of histone H4 can stimulate the activity of yeast Dot1 in a specific manner, which coordinates with histone H2B ubiquitination to affect H3K79 methylation. H4K16ac and H2BUb play crucial roles in histone cross-talk, regulating gene transcription and gene silencing together.
Article
Biochemistry & Molecular Biology
Zhiheng Deng, Huasong Ai, Maoshen Sun, Zebin Tong, Yunxiang Du, Qian Qu, Liying Zhang, Ziyu Xu, Shixian Tao, Qiang Shi, Jia-Bin Li, Man Pan, Lei Liu
Summary: This study elucidates the mechanism of H2B monoubiquitylation and highlights the critical role of nucleosomal DNA in mediating E3 ligase recognition.
Article
Multidisciplinary Sciences
Weiye Zhao, Ying Xu, Yufan Wang, Dan Gao, Jasmine King, Yajie Xu, Fu-Sen Liang
Summary: The research uncovered the relationship between H3K27ac and H3K4me3 in the gene activation process using CRISPR/dCas-based epigenome editing methods, demonstrating the crosstalk between epigenetic mechanisms.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Prince Verma, Court K. M. Waterbury, Elizabeth M. Duncan
Summary: By analyzing the H3K4me3 signal on the planarian genome, it was found that Set1 plays a key role in creating this mark, with its depletion leading to abnormal stem cell phenotypes suggesting dysfunction of TSGs.
Article
Genetics & Heredity
Richard A. Kleinschmidt, Laurie M. Lyon, Samantha L. Smith, Jonah Rittenberry, K. Maeve Lawless, Anabelle A. Acosta, David Donze
Summary: Several studies have found that deletion or mutation of the histone deacetylase (HDAC) gene RPD3 in Saccharomyces cerevisiae results in increased heterochromatic gene silencing at specific loci. Through a genetic screen for suppressors of this extended silencing phenotype at the HMR locus, mutations in the histone H3 lysine 4 methylation (H3K4me) pathway were identified as specific to the rpd3 Delta extended silencing phenotype. Moreover, the RNA Polymerase III complex remains bound and active at the HMR-tDNA in rpd3 mutants despite extended silencing, suggesting a unique regulatory mechanism.
G3-GENES GENOMES GENETICS
(2021)
Review
Endocrinology & Metabolism
Lindsay Moritz, Saher Sue Hammoud
Summary: This article explores the molecular mechanisms underlying male fertility and the process of chromatin remodeling. It points out the current gaps in understanding of the chromatin remodeling process and suggests future research directions to enhance our knowledge of the histone-to-protamine exchange and the etiology of idiopathic male infertility.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Multidisciplinary Sciences
Yusuke Fujiwara, Yuki Yamanashi, Akiko Fujimura, Yuko Sato, Tomoya Kujirai, Hitoshi Kurumizaka, Hiroshi Kimura, Kenzo Yamatsugu, Shigehiro A. Kawashima, Motomu Kanai
Summary: The study developed a chemical catalyst that can achieve histone acetylation in living cells without genetic manipulation, offering a new tool for studying epigenetic regulation. This chemical method competes with and suppresses normal chromatin function markers, providing insights into epigenetic mechanisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Franziska Greulich, Michael Wierer, Aikaterini Mechtidou, Omar Gonzalez-Garcia, N. Henriette Uhlenhaut
Summary: The SETD1A/COMPASS histone methyltransferase complex is highly enriched in activated mouse macrophages and cooperates with the glucocorticoid receptor (GR) to mediate anti-inflammatory effects. Their interaction leads to transcriptional changes in subsets of macrophage target genes.
Article
Biochemical Research Methods
Soumya Mukherjee, Andris Jankevics, Florian Busch, Markus Lubeck, Yang Zou, Gary Kruppa, Albert J. R. Heck, Richard A. Scheltema, Karli R. Reiding
Summary: Ion mobility enables spatial separation of ions in the gas phase, providing information about their size. The timsTOF Pro device can physically separate N-glycopeptides from nonmodified peptides and produce high-quality fragmentation spectra. This method allows for the effective selection of analytes of interest based on the clear cluster in the mobiologram formed by the glycan moieties enlarging the size of glycopeptides.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Biochemical Research Methods
Wouter van Bergen, Johannes F. Hevler, Wei Wu, Marc P. Baggelaar, Albert J. R. Heck
Summary: Most drugs target proteins, and determining the exact drug binding sites on proteins is crucial for understanding their effects. A strategy called PhosID-ABPP was developed to identify drug binding sites using immobilized metal-affinity chromatography and phosphonate affinity tags. This method successfully identified over 500 unique binding sites of the drug PF-06672131. PhosID-ABPP also revealed differences in binding sites between intact cells and cell lysates, and captured a previously elusive binding site on the epidermal growth factor receptor.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Review
Chemistry, Multidisciplinary
Evolene Desligniere, Amber Rolland, Eduard H. T. M. Ebberink, Victor Yin, Albert J. R. Heck
Summary: Native mass spectrometry is widely used for determining the mass of intact proteins and their biomolecular assemblies. However, it can be challenging for heterogeneous protein complexes. In 2012, an Orbitrap-based mass analyzer with extended mass range was introduced, enabling high-resolution mass spectra of large protein assemblies and single ion measurements. This led to the development of single-molecule Orbitrap-based charge detection mass spectrometry in 2020, which has opened doors for innovative research in various systems.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Chemistry, Analytical
Fujia Wang, Tim Veth, Marije Kuipers, Maarten Altelaar, Kelly E. Stecker
Summary: A successful mass spectrometry-based phosphoproteomics analysis relies on effective sample preparation strategies. The performance of the S-Trap protocol for phosphoproteomics studies is unclear, and the addition of phosphoric acid (PA) in the existing protocol is detrimental to downstream phosphopeptide enrichment. This study systematically evaluates the performance of the S-Trap digestion for proteomics and phosphoproteomics, and demonstrates that an optimized S-Trap approach, with trifluoroacetic acid substituted for PA, is a simple and effective method for phosphoproteomics sample preparation.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Melina Blanco, Laila El Khattabi, Clara Gobe, Marion Crespo, Manon Coulee, Alberto de la Iglesia, Come Ialy-Radio, Clementine Lapoujade, Maelle Givelet, Marion Delessard, Ivan Seller-Corona, Kosuke Yamaguchi, Nadege Vernet, Fred Van Leeuwen, Alban Lermine, Yuki Okada, Romain Daveau, Rafael Oliva, Pierre Fouchet, Ahmed Ziyyat, Delphine Pflieger, Julie Cocquet
Summary: In this study, it is found that the H3K79-methyltransferase DOT1L plays a crucial role in spermatid chromatin remodeling and gene expression regulation. The knockout of the Dot1l gene in mice resulted in less compact chromatin structure and abnormal content in spermatozoa, including the presence of transition proteins, immature protamine 2 forms, and higher levels of histones. Additionally, the Dot1l knockout also caused less compact heads and decreased motility in spermatozoa, leading to impaired fertility.
Article
Biochemistry & Molecular Biology
Ineke Brouwer, Emma Kerklingh, Fred van Leeuwen, Tineke L. Lenstra
Summary: Using single-molecule live-cell imaging, Brouwer et al. investigate how the remodeling of promoter nucleosomes regulates transcriptional bursting. They find that at the Gal4 binding sites, RSC and Gal4 binding synergistically facilitate each burst. In contrast, nucleosome remodeling at the TATA box controls only the first burst upon galactose induction. The results reveal the importance of promoter nucleosome remodeling in regulating the kinetics of transcription.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Andrology
Min Zhang, Riccardo Zenezini Chiozzi, Elizabeth G. Bromfield, Albert J. R. Heck, J. Bernd Helms, Bart M. Gadella
Summary: This study aimed to identify the interacting partners of CRISP2. The interactions of these binding partners were investigated under different conditions. The results suggest that CRISP2 may act as a scaffold for protein complex formation and dissociation to ensure the correct positioning of proteins required for the acrosome reaction and zona pellucida penetration.
Article
Biology
Leire Aguinagalde Salazar, Maurits A. den Boer, Suzanne M. Castenmiller, Seline A. Zwarthoff, Carla de Haas, Piet C. Aerts, Frank J. Beurskens, Janine Schuurman, Albert J. R. Heck, Kok van Kessel, Suzan H. M. Rooijakkers
Summary: In this study, it is found that by modifying the structure of monoclonal antibodies (mAbs), the immune protection and bactericidal effect against Streptococcus pneumoniae can be improved. The modified mAbs effectively activate the complement system and recruit complement component C1 for bacterial clearance, enhancing the antibacterial activity against various serotypes of pneumococci. This study provides an important proof of concept for the future development of antibody therapies against encapsulated bacteria.
Article
Biotechnology & Applied Microbiology
Yen-Hsi Chen, Weihua Tian, Makiko Yasuda, Zilu Ye, Ming Song, Ulla Mandel, Claus Kristensen, Lorenzo Povolo, Andre R. A. Marques, Tomislav Caval, Albert J. R. Heck, Julio Lopes Sampaio, Ludger Johannes, Takahiro Tsukimura, Robert Desnick, Sergey Y. Y. Vakhrushev, Zhang Yang, Henrik Clausen
Summary: Currently available enzyme replacement therapies for lysosomal storage diseases are limited in their effectiveness due to short circulation times and suboptimal biodistribution of the therapeutic enzymes. Researchers have engineered Chinese hamster ovary (CHO) cells to produce glycoengineered enzymes, which have improved circulation time and biodistribution. This glycoengineering approach, known as Long-Acting-GlycoDesign (LAGD), may be widely applicable to lysosomal replacement enzymes to improve their circulatory stability and therapeutic efficacy.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Oncology
Beiping Miao, Zhaoqing Hu, Riccardo Mezzadra, Lotte Hoeijmakers, Astrid Fauster, Shangce Du, Zhi Yang, Melanie Sator-Schmitt, Helena Engel, Xueshen Li, Caroline Broderick, Guangzhi Jin, Raquel Gomez-Eerland, Lisette Rozeman, Xin Lei, Hitoshi Matsuo, Chen Yang, Ingrid Hofland, Dennis Peters, Annegien Broeks, Elke Laport, Annika Fitz, Xiyue Zhao, Mohamed A. A. Mahmoud, Xiujian Ma, Sandrine Sander, Hai-kun Liu, Guoliang Cui, Yu Gan, Wei Wu, Yanling Xiao, Albert J. R. Heck, Wenxian Guan, Scott W. Lowe, Hugo M. Horlings, Cun Wang, Thijn R. Brummelkamp, Christian U. Blank, Ton N. M. Schumacher, Chong Sun
Summary: The dysregulation of immune checkpoint molecules allows cancer cells to escape immune destruction. CD58, an important costimulatory ligand, is found to be positively regulated by CMTM6, which also interacts with PD-L1. The presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and the response to PD-L1-PD-1 blockade.
Article
Cell Biology
Dusanka Milenkovic, Jelena Misic, Johannes F. Hevler, Thibaut Molinie, Injae Chung, Ilian Atanassov, Xinping Li, Roberta Filograna, Andrea Mesaros, Arnaud Mourier, Albert J. R. Heck, Judy Hirst, Nils-Goran Larsson
Summary: The mammalian respiratory chain complexes CI, CIII2, and CIV form a stable assembly called the respirasome, which is critical for cellular bioenergetics. By studying knockin mice with decreased levels of respirasomes, researchers found that high levels of respirasomes are dispensable for maintaining bioenergetics and physiology in mice. However, the alternate functions of respirasomes, such as regulating protein stability and preventing age-associated protein aggregation, need further investigation.
Article
Oncology
Marjolein C. Stip, Mitchell Evers, Maaike Nederend, Chilam Chan, Karli R. Reiding, Mirjam J. Damen, Albert J. R. Heck, Sofia Koustoulidou, Ruud Ramakers, Gerard C. Krijger, Remmert de Roos, Edouard Souteyrand, Annelisa M. Cornel, Miranda P. Dierselhuis, Marco Jansen, Mark de Boer, Thomas Valerius, Geert van Tetering, Jeanette H. W. Leusen, Friederike Meyer-Wentrup
Summary: Researchers engineered an antibody called IgA3.0 ch14.18, which shows promise as a new therapy for neuroblastoma. The antibody has a longer half-life, increased protein stability, and potent tumor-killing abilities.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Cell Biology
Donna O. Debets, Kelly E. Stecker, Anastasia Piskopou, Marte C. Liefaard, Jelle Wesseling, Gabe S. Sonke, Esther H. Lips, Maarten Altelaar
Summary: This study performs (phospho)proteomics analysis of pre-treatment HER2+ needle biopsies of early-stage invasive breast cancer to identify molecular signatures predictive of treatment response. The study finds that accurate quantification of the estrogen receptor (ER) and HER2 biomarkers, along with the assessment of associated biological features, can improve treatment outcome prediction. Additionally, the study identifies cellular mechanisms that potentially precondition tumors to resist therapy.
CELL REPORTS MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Inge Gazi, Karli R. Reiding, Andre Groeneveld, Jan Bastiaans, Thom Huppertz, Albert J. R. Heck
Summary: We monitored the changes in bovine milk IgG over a 28-day period after calving, finding that IgG accounts for over 50% of protein content in colostrum but less than 3% in mature milk. The N-glycosylation profile of bovine milk IgG was found to be highly heterogeneous with over 40 glycoforms, and this profile changed significantly during lactation. We also identified the presence of IgG3 subtype in bovine milk, alongside IgG1 and IgG2. These findings are important for understanding calf's immune development and the nutritional value of bovine milk.
Article
Immunology
Kelly A. Dingess, Max Hoek, Danique M. H. van Rijswijk, Sem Tamara, Maurits A. den Boer, Tim Veth, Mirjam J. A. Damen, Arjan Barendregt, Michelle Romijn, Hannah G. Juncker, Britt J. van Keulen, Gestur Vidarsson, Johannes B. van Goudoever, Albert Bondt, Albert J. R. Heck
Summary: The most abundant immunoglobulin in the human body is IgA and it is found in high concentrations in mucosal lining and biofluids like milk. The structure and clonal repertoire of IgA1-containing molecular assemblies were analyzed using mass spectrometry-based approach in serum and milk from three donors. The results showed that serum IgA1 consists of two distinct structural populations, monomeric IgA1 and dimeric J-chain coupled IgA1, while IgA1 in milk is present only as secretory IgA (SIgA) with various assemblies. The IgA1-Fab repertoires in serum and milk were also found to be different.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
