Article
Biophysics
Jialin Chen, Xiushuang Yuan, Peng Wei, Daoping Wang, Chen Chen, Quanqiang Guo, Shi-Zhong Luo, Long Chen
Summary: This study investigates the effects of TAF15-PrLD mutations on amyloid fibril formation and identifies an important beta-amyloid-forming segment in TAF15-PrLD. A pathogenic mutation T2 E71G enhances the aggregation of TAF15-PrLD segment T2, and the T2 peptide induces a phase transition in TAF15-PrLD protein. The SGYS motif is identified as a critical segment promoting amyloid fibril formation.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Eleonora Stronati, Stefano Biagioni, Mario Fiore, Mauro Giorgi, Giancarlo Poiana, Camilla Toselli, Emanuele Cacci
Summary: Research shows that mutations in FUS are associated with ALS, impacting the proliferation and differentiation of neural stem cells, leading to a preference for glial cell lineage development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Ling Tao, Myrthala Moreno-Smith, Rodrigo Ibarra-Garcia-Padilla, Giorgio Milazzo, Nathan A. Drolet, Blanca E. Hernandez, Young S. Oh, Ivanshi Patel, Jean J. Kim, Barry Zorman, Tajhal Patel, Abu Hena Mostafa Kamal, Yanling Zhao, John Hicks, Sanjeev A. Vasudevan, Nagireddy Putluri, Cristian Coarfa, Pavel Sumazin, Giovanni Perini, Ronald J. Parchem, Rosa A. Uribe, Eveline Barbieri
Summary: This study shows that CHAF1A gain-of-function supports cell malignancy, blocks neuronal differentiation, and promotes NB oncogenesis. Mechanistically, CHAF1A upregulates polyamine metabolism, which blocks neuronal differentiation and promotes cell cycle progression.
Article
Cell Biology
Lydia M. M. Parkinson, Sarah L. L. Gillen, Laura M. M. Woods, Lewis Chaytor, Daniel Marcos, Fahad R. R. Ali, Jason S. S. Carroll, Anna Philpott
Summary: ASCL1 plays a role in maintaining proliferation and controlling differentiation in neuroblastoma cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yan-Rong Feng, Sayed Haidar Abbas Raza, Cheng-Cheng Liang, Xiao-Yu Wang, Jian-Fang Wang, Wen-Zheng Zhang, Linsen Zan
Summary: CREB1 plays an important role in Qinchuan bovine skeletal myoblasts, promoting cell proliferation and differentiation by mediating the transcription of CCNA2 and MyoG. It is involved in cell proliferation, myogenic differentiation, and skeletal muscle repair pathways.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Cell & Tissue Engineering
Padmina Shrestha, Anbalagan Jaganathan, Dhananjay Huilgol, Carlos Ballon, Yon Hwangbo, Alea A. Mills
Summary: Chd5 is an ATP-dependent chromatin remodeler that promotes neuronal differentiation, but its mechanism in neurogenesis is not well understood. Through transcriptional profiling of Chd5 deficient mice, we found that Chd5 regulates neurogenesis by directing stepwise transcriptional changes. Chd5 promotes the expression of Six3, a proneural transcription factor, to repress the non-canonical Wnt ligand Wnt5a during early stages of neurogenesis. This ability of Chd5 to transcriptionally repress neuronal maturation factors is critical for both lineage specification and maturation.
Article
Biochemistry & Molecular Biology
Daniel J. Garcia-Dominguez, Nabil Hajji, Sara Sanchez-Molina, Elisabet Figuerola-Bou, Rocio M. de Pablos, Ana M. Espinosa-Oliva, Eduardo Andres-Leon, Laura Carmen Terron-Camero, Rocio Flores-Campos, Guillem Pascual-Pasto, Maria Jose Robles, Angel M. Carcaboso, Jaume Mora, Enrique de Alava, Lourdes Hontecillas-Prieto, Isidro Machado, Antonio Llombart-Bosch, Giovanna Magagnoli, Katia Scotlandi
Summary: The study reveals that HDAC6 plays a regulatory role in EWS, and selective inhibition of HDAC6 can reduce the oncogenic functions of EWSR1-FLI1. High expression of HDAC6 is associated with poor prognosis in EWS patients, and a combination treatment of HDAC6 and doxorubicin significantly inhibits tumor growth in EWS models.
Article
Biochemistry & Molecular Biology
Noel Blanco-Tourinan, Hector H. Torres-Martinez, Frauke Augstein, Chloe Champeyroux, Claudia von der Mark, Annelie Carlsbecker, Joseph G. Dubrovsky, Antia Rodriguez-Villalon
Summary: The connection between the vasculature of the primary root and the emerging lateral roots is established through coordinated actions of the procambium and pericycle. The formation of a xylem bridge, consisting of xylem cells derived from the procambium and pericycle, is crucial for this vascular connectivity. Transcription factors and the deposition of secondary cell walls play important roles in the specification and differentiation of the xylem bridge.
Article
Nanoscience & Nanotechnology
Shintaro Yamaguchi, Ryo Isaka, Yuji Sakahashi, Hirofumi Tsujino, Yuya Haga, Kazuma Higashisaka, Yasuo Tsutsumi
Summary: Research has found that silver nanoparticles with a diameter of 10 nm can inhibit retinoic acid-induced neuronal differentiation. This inhibitory effect may be achieved through the oxidative stress pathway, induction of mitochondrial ROS production, and decreased expression of mitochondrial fusion-related genes.
ACS APPLIED NANO MATERIALS
(2022)
Article
Biochemical Research Methods
Samiksha Sardana, Anneroos E. Nederstigt, Marc P. Baggelaar
Summary: S-palmitoylation is a lipid modification that plays a role in neuronal development and neurodegenerative diseases. In this study, two methods were used to identify S-palmitoylated proteins and sites during neuronal differentiation. A subset of high-confidence S-palmitoylated proteins were identified, suggesting an important role for S-palmitoylation in neuronal differentiation.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Multidisciplinary Sciences
Kanita A. Chaudhry, Justine J. Jacobi, Bryan M. Gillard, Ellen Karasik, Jeffrey C. Martin, Tatiane da Silva Fernandes, Edward Hurley, Maria Laura Feltri, Kristopher M. Attwood, Clare J. Twist, Dominic J. Smiraglia, Mark D. Long, Anna Bianchi-Smiraglia
Summary: This study identifies the aryl hydrocarbon receptor (AhR) as a transcription factor promoting the growth and suppressing the differentiation of MYCN-amplified neuroblastoma. AhR antagonism, combined with retinoic acid, may result in a more durable response in patients.
Article
Neurosciences
Begum Aydin, Michael Sierk, Mireia Moreno-Estelles, Link Tejavibulya, Nikathan Kumar, Nuria Flames, Shaun Mahony, Esteban O. Mazzoni
Summary: Forced expression of transcription factors (TFs) can program neuronal fate, but the mechanisms underlying TF coordination and control of distinct neuronal fates are still unclear. Using neuronal programming of embryonic stem cells, this study found that the addition of TFs can redirect neuron fate. Specifically, the TF combination of Ascl1-Lmx1b-Foxa2-Pet1 leads to a diffuse monoaminergic fate. The pioneer factor Foxa2 represses Phox2b to induce serotonergic fate, and Foxa2 and Pet1 synergistically upregulate serotonergic fate.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Haiyuan Ren, Jinrui Li, Ai Peng, Ting Liu, Mengjun Chen, Hongguang Li, Xiaojing Wang
Summary: In this study, a water-soluble fullerene C-60 derivative bearing alanine residues (Ala-C-60) was synthesized and its effects on neural stem cells (NSCs) were explored. The results showed that Ala-C-60 can promote the proliferation and differentiation of NSCs into neurons, and inhibit their migration. Furthermore, it significantly increased the cell viability of NSCs treated with hydrogen peroxide.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Carlos Jimenez, Roberta Antonelli, Marc Masanas, Aroa Soriano, Laura Devis-Jauregui, Jessica Camacho, Ainara Magdaleno, Gabriela Guillen, Raquel Hladun, Luz Jubierre, Josep Roma, David Llobet-Navas, Josep Sanchez de Toledo, Lucas Moreno, Soledad Gallego, Miguel F. Segura
Summary: Neuroblastoma is a common pediatric tumor with epigenetic deregulation playing a significant role in its aggressive behavior. Research suggests that ZRF1, an epigenetic regulator, may not directly impact neuroblastoma cells but its mRNA expression levels could be used as an independent prognostic factor for patient survival.
Article
Biochemistry & Molecular Biology
Eisaku Ogawa, Tomohiro Edamitsu, Hidetaka Ohmori, Kazuyoshi Kohu, Mineo Kurokawa, Hiroshi Kiyonari, Masanobu Satake, Ryuhei Okuyama
Summary: This study reveals the important roles of Runx1 and Runx3 in keratinocyte differentiation, where they directly inhibit the expression of keratin 1 and keratin 10 genes during the differentiation process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Andrea Cipriano, Martina Macino, Giulia Buonaiuto, Tiziana Santini, Beatrice Biferali, Giovanna Peruzzi, Alessio Colantoni, Chiara Mozzetta, Monica Ballarino
Summary: This study identified a novel lncRNA, Lnc-Rewind, which regulates MuSC proliferation and expansion by influencing the expression of skeletal muscle genes and components of the WNT signaling pathway in mouse. The interaction of Lnc-Rewind with the G9a histone lysine methyltransferase mediates the repression of the Wnt7b gene, providing insights into the epigenetic regulation of adult muscle stem cells fate by lncRNAs.
Article
Neurosciences
Anchel Gonzalez-Barriga, Louison Lallemant, Diana M. Dinca, Sandra O. Braz, Helene Polveche, Paul Magneron, Cedric Pionneau, Aline Huguet-Lachon, Jean-Baptiste Claude, Cerina Chhuon, Ida Chiara Guerrera, Cyril F. Bourgeois, Didier Auboeuf, Genevieve Gourdon, Mario Gomes-Pereira
Summary: Myotonic dystrophy type 1 is a neuromuscular disorder caused by non-coding CTG repeat expansion in the DMPK gene, generating toxic CUG RNA that interferes with RNA processing in multiple tissues. The impact of expanded CUG RNA on glial cells is more significant than on neuronal cells, suggesting impaired cell differentiation. This study provides insights into the molecular events of RNA toxicity in the CNS with a focus on non-neuronal mechanisms and proteomic changes in DM1 brain disease.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Evelyne Manet, Helene Polveche, Fabrice Mure, Paulina Mrozek-Gorska, Florian Roisne-Hamelin, Wolfgang Hammerschmidt, Didier Auboeuf, Henri Gruffat
Summary: This study systematically analyzed the time-resolved expression of cellular mRNA splice variants during EBV infection of resting B lymphocytes. The results showed that major modifications in alternative splice variant expression occurred as early as day 1 post-infection, indicating that splicing regulation, in addition to transcription, provides an additional mechanism of gene expression regulation at the onset of B cell activation and proliferation.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Didier Auboeuf
Summary: Life emerged from the coupling between nucleic acid and protein synthesis, maintaining physicochemical parameter equilibria for proto-genomes, which evolved depending on biological activities in response to environmental fluctuations. Evolution depends on bidirectional relationship between genome and phenotype, with phenotype interacting with the environment to direct genome evolution.
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
(2021)
Review
Cell Biology
Giulia Buonaiuto, Fabio Desideri, Valeria Taliani, Monica Ballarino
Summary: The potential of RNA as a therapeutic tool has attracted public attention, with its single-stranded nature and ease of in vitro synthesis making it the most suitable tool for drug development. Non-coding RNAs are emerging as multifaceted regulators, showing therapeutic potential in tissue repair and regeneration.
Article
Multidisciplinary Sciences
Margot Jarrige, Helene Polveche, Alexandre Carteron, Stephane Janczarski, Marc Peschanski, Didier Auboeuf, Cecile Martinat
Summary: Human pluripotent stem cells have brought forth a new era in disease modeling, drug discovery, and cell therapy development. SISTEMA, a curated gene expression database, serves as a one-stop resource for the stem cell community to easily evaluate gene expression levels and compare them across different conditions.
Article
Biochemistry & Molecular Biology
Elisabeth Scheer, Jie Luo, Andrea Bernardini, Frank Ruffenach, Jean-Marie Garnier, Isabelle Kolb-Cheynel, Kapil Gupta, Imre Berger, Jeff Ranish, Laszlo Tora
Summary: TFIID, a human general transcription factor, consists of TBP and 13 TAFs, playing a crucial role in Pol II transcription. Assembly of a 5TAF core complex in vitro serves as a building block for forming lobe A or B in TFIID. TAF8 contains distinct regions critical for assembling with the 5TAF core complex in lobe B and interacting with TAF2 in lobe C, both essential for mouse ESC survival.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Karima Habbas, Oktay Cakil, Boglarka Zambo, Ricardos Tabet, Fabrice Riet, Doulaye Dembele, Jean-Louis Mandel, Michael Hocquemiller, Ralph Laufer, Francoise Piguet, Herve Moine
Summary: Fragile X syndrome (FXS) is a common form of familial intellectual disability caused by the lack of RNA-binding protein FMRP. This study demonstrates that DGKk, an mRNA target of FMRP and a regulator of lipid signaling, plays an important role in FXS pathogenesis, and the delivery of modified and FMRP-independent DGKk can correct abnormal lipid signaling and behavioral phenotypes in FXS mice.
EMBO MOLECULAR MEDICINE
(2022)
Article
Oncology
Anne-Sophie Hatat, Clara Benoit-Pilven, Amelie Pucciarelli, Florence de Fraipont, Lucie Lamothe, Pascal Perron, Amandine Rey, Matteo Giaj Levra, Anne-Claire Toffart, Didier Auboeuf, Beatrice Eymin, Sylvie Gazzeri
Summary: This study identifies an alternative splicing event involving the autophagic gene ATG16-L1 as a potential mechanism for acquired resistance to EGFR-TKIs in NSCLC. Overexpression of the splice variant ATG16-L1 beta was found to be associated with resistance to EGFR-TKI treatment. Mechanistically, ATG16-L1 beta impairs gefitinib-induced autophagy, leading to cell survival and resistance. Neutralization of ATG16-L1 beta restores autophagy and sensitizes cells to gefitinib-induced apoptosis. These findings highlight the importance of splicing regulation in EGFR-targeted cancer therapy.
MOLECULAR ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Veronique Fischer, Vincent Hisler, Elisabeth Scheer, Elisabeth Lata, Bastien Morlet, Damien Plassard, Dominique Helmlinger, Didier Devys, Laszlo Tora, Stephane D. Vincent
Summary: The coactivator complex SAGA plays a vital role in regulating chromatin accessibility and transcription. The presence of SUPT3H is not essential for overall Pol II transcription, but is required for the growth and self-renewal of mouse embryonic stem cells. Loss of SUPT3H only affects the transcription of a specific subset of genes, suggesting that yeast and mammalian SAGA complexes have distinct mechanisms of transcription regulation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biology
Marjorie Fournier, Amelie Rodrigue, Larissa Milano, Jean-Yves Bleuyard, Anthony M. Couturier, Jacob Wall, Jessica Ellins, Svenja Hester, Stephen J. Smerdon, Laszlo Tora, Jean-Yves Masson, Fumiko Esashi
Summary: The tumour suppressor PALB2 stimulates homologous recombination (HR) repair of DNA damage and protects active genes during DNA replication. Acetylation of the 7K-patch within the PALB2 chromatin association motif (ChAM) by KAT2A/2B enhances PALB2's association with nucleosomes. DNA damage triggers deacetylation of ChAM and increases PALB2's mobility. Mutations in the 7K-patch affect PALB2's chromatin binding, leading to defects in RAD51 foci formation and decreased cell survival.
Article
Biochemistry & Molecular Biology
Andrea Bernardini, Pooja Mukherjee, Elisabeth Scheer, Ivanka Kamenova, Simona Antonova, Paulina Karen Mendoza Sanchez, Gizem Yayli, Bastien Morlet, H. T. Marc Timmers, Laszlo Tora
Summary: In this study, the authors investigate the co-translational assembly pathway of the TFIID complex by using RNA-immunoprecipitation, single-molecule imaging, and proteomics. They discover that TAF1 plays a critical role in TFIID assembly by serving as a flexible scaffold for the co-translational recruitment of preassembled submodules. These findings provide insights into the biogenesis of TFIID and potentially other large protein complexes.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Cell Biology
Gizem Yayli, Andrea Bernardini, Paulina Karen Mendoza Sanchez, Elisabeth Scheer, Mylene Damilot, Karim Essabri, Bastien Morlet, Luc Negroni, Stephane D. Vincent, H. T. Marc Timmers, Laszlo Tora
Summary: This study uncoveres the assembly mechanism of ATAC and SAGA co-activator complexes and reveals the distinct subcellular localization and functions between them.
Review
Biochemistry & Molecular Biology
Farrah El-Saafin, Didier Devys, Steven A. Johnsen, Stephane D. Vincent, Laszlo Tora
Summary: Ubiquitin is a highly conserved protein expressed in eukaryotic cells and plays a role in post-translational modification. It can be added to proteins either in a monoubiquitination or polyubiquitination manner. Monoubiquitination acts as a signaling mark to regulate various biological processes. The cellular distribution of ubiquitin is determined by the activity of ligase enzymes and deubiquitinases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Liliana Arede, Elena Foerner, Selinde Wind, Rashmi Kulkarni, Ana Filipa Domingues, George Giotopoulos, Svenja Kleinwaechter, Maximilian Mollenhauer-Starkl, Holly Davison, Aditya Chandru, Ryan Asby, Ralph Samarista, Shikha Gupta, Dorian Forte, Antonio Curti, Elisabeth Scheer, Brian J. P. Huntly, Laszlo Tora, Cristina Pina
Summary: Epigenetic histone modifiers play key roles in regulating cell fate decisions in normal and malignant hematopoiesis. This study focuses on KAT2A, a lysine acetyltransferase, and explores its involvement in different macromolecular complexes and their distinct molecular and cellular consequences. The study identifies the contributions of ATAC and SAGA complexes in regulating biosynthetic activity and cell type-specific programs, providing insights into the requirements of KAT2A in leukemia and erythroid lineage specification and development.