Article
Neurosciences
Sajad Hamid Ahanger, Ryan N. Delgado, Eugene Gil, Mitchel A. Cole, Jingjing Zhao, Sung Jun Hong, Arnold R. Kriegstein, Tomasz J. Nowakowski, Alex A. Pollen, Daniel A. Lim
Summary: This study utilized GO-CaRT technology to investigate genome architecture in neural precursors, revealing the relationship between LAD architecture and regional identity of neural precursor cells, as well as identifying transcriptionally highly active sub-domains within LADs. Additionally, the study found speckle-associated domains to be enriched for genetic loci associated with schizophrenia risk.
NATURE NEUROSCIENCE
(2021)
Article
Acoustics
Houxin She, Chaofeng Li, Qiansheng Tang, Bangchun Wen
Summary: This study investigates the eigenvalues of veering and merging phenomena in an assembly bladed disk system, as well as the interactions between disk-dominated and blade-dominated modes. Through numerical analysis using modal functions and frequency-domain methods, it is found that coupling interactions induce various phenomena, with modal frequencies at low rotational speeds significantly affected by nonlinearity.
JOURNAL OF SOUND AND VIBRATION
(2021)
Article
Multidisciplinary Sciences
Hua-Jun Wu, Alexandro Landshammer, Elena K. Stamenova, Adriano Bolondi, Helene Kretzmer, Alexander Meissner, Franziska Michor
Summary: The disruption of a SOX17 boundary in human pluripotent stem cells interferes with proper differentiation, and germline variations affecting such boundaries are selectively retained, leading to underrepresentation in the human population.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Taryn J. J. Olivas, Yumei Wu, Shenliang Yu, Lin Luan, Peter Choi, Emily D. D. Guinn, Shanta Nag, Pietro V. V. De Camilli, Kallol Gupta, Thomas J. J. Melia
Summary: ATG9 vesicles serve as the membrane seed for mammalian autophagosomes, as shown by Olivas et al. using nanodisc technology. The integration of ATG9 with expanding autophagosome membranes demonstrates the importance of lipid transfer in autophagosome expansion. This work provides significant insights into the model of autophagosome formation and expands our understanding of the cellular process of autophagy.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Mayank N. K. Choudhary, Kara Quaid, Xiaoyun Xing, Heather Schmidt, Ting Wang
Summary: Transposable elements (TEs), previously considered as junk DNA, contribute to species-specific 3D-genome structure by providing binding sites for CTCF protein. These elements play a role in gene regulation during mammalian evolution.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Evonne McArthur, John A. Capra
Summary: Topologically associating domains (TADs) and TAD boundaries play crucial roles in gene regulation, rare-disease pathogenesis, and the genetic contribution to complex diseases. TAD boundaries are more constrained by genetic variation and evolutionary pressure compared to TADs, and they have a greater impact on heritability of traits related to immunology, hematology, and metabolism. The stability of TAD boundaries across cell types provides valuable insights into the functional landscape of the genome and enhances variant interpretation by considering 3D structure.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Wilfried M. Guiblet, Marzia A. Cremona, Robert S. Harris, Di Chen, Kristin A. Eckert, Francesca Chiaromonte, Yi-Fei Huang, Kateryna D. Makova
Summary: Approximately 13% of the human genome can fold into non-canonical (non-B) DNA structures, which have been implicated in vital cellular processes. Non-B DNA hinders replication, increasing errors and facilitating mutagenesis, yet its contribution to genomewide variation in mutation rates remains unexplored. Non-B DNA substantially contributes to variation in substitution frequencies at small and large scales, highlighting its role in germline mutagenesis with implications to evolution and genetic diseases.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Cynthia A. Kalita, Alexander Gusev
Summary: DeCAF is a new method proposed to identify cell-fraction QTLs in tumors by leveraging both allelic and total expression information. Applied to RNA-seq data from TCGA, DeCAF discovered 3664 genes with cfQTLs in 14 cell types, representing a 5.63-fold increase compared to conventional interaction-eQTL mapping.
Article
Multidisciplinary Sciences
Javier Arpon, Kaori Sakai, Valerie Gaudin, Philippe Andrey
Summary: Spatial organization in biological systems plays a crucial role in determining relative positioning and spatial patterns of components. However, biological variability and the lack of appropriate statistical methods hinder the analysis of these interactions.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Bertille Montibus, Jil Cercy, Tristan Bouschet, Amandine Charras, Stephanie Maupetit-Mehouas, David Nury, Celine Gonthier-Gueret, Sabine Chauveau, Nicolas Allegre, Caroline Chariau, Charles C. Hong, Isabelle Vaillant, C. Joana Marques, Franck Court, Philippe Arnaud
Summary: The induction of Kdm6b expression upon neural commitment of mouse embryonic stem cells is linked to rearrangement between two 3D configurations defined by the promoter contact with different regions in the Kdm6b locus. This rearrangement is associated with changes in 5-hydroxymethylcytosine (5hmC) levels and requires the functional ten-eleven-translocation (TET) 3 protein. This reveals an unexpected interplay between the 5-hmC and H3K27me3 pathways during neural lineage commitment in mammals.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Multidisciplinary Sciences
Benjamin D. Weger, Cedric Gobet, Fabrice P. A. David, Florian Atger, Eva Martin, Nicholas E. Phillips, Aline Charpagne, Meltem Weger, Felix Naef, Frederic Gachon
Summary: The study investigated the roles of the circadian clock and feeding rhythms in regulating rhythmic gene expression in the liver, highlighting their importance and differential contributions. Both feeding patterns and the circadian clock influence gene expression rhythms, with distinct amplitudes. By analyzing multiple core clock regulators, the research revealed their varying impacts on liver gene expression regulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Surgery
Marine Cossec, Florian Atger, Claire Blanchard, David Jacobi
Summary: The timing of food intake can affect circadian rhythms and metabolism, potentially impacting obesity. Studies suggest a correlation between meal timing and weight loss after bariatric surgery in adults, with evidence pointing towards late-night food consumption hindering weight loss progress.
Article
Biochemistry & Molecular Biology
Florian Rosier, Audrey Brisebarre, Claire Dupuis, Sabrina Baaklini, Denis Puthier, Christine Brun, Lydie C. Pradel, Pascal Rihet, Didier Payen
Summary: Through two genome-wide association studies, the research identified an association between SNP within the CISH gene and death in septic shock patients. Further investigation revealed rs143356980 as a key regulatory candidate that modulates pathways related to death, increasing the risk of mortality in patients with septic shock.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Manon Durand, Marine Coue, Mikael Croyal, Thomas Moyon, Angela Tesse, Florian Atger, Khadija Ouguerram, David Jacobi
Summary: NAFLD is a dysmetabolic hepatic damage that progresses through stages of increasing severity, with oxidative stress and specific hepatic lipid species playing potential roles in disease progression. A study on mouse livers with NAFLD induced by a western diet revealed time-dependent changes in mitochondrial lipid composition, suggesting mitochondrial lipid modifications may act as an early event in mitochondrial dysfunction and disease progression.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2021)
Article
Biology
Hala Al Adhami, Anais Flore Bardet, Michael Dumas, Elouan Cleroux, Sylvain Guibert, Patricia Fauque, Herve Acloque, Michael Weber
Summary: This study investigates the distribution and function of DNA methylation in different vertebrate species, revealing both conservation and divergence in methylation patterns and functions. The study shows that the chicken genome has lower levels of methylation compared to other species and other species exhibit a higher frequency of CpG-rich DNA methylation compared to mice. The study also demonstrates the conservation of DNA methylation in silencing germline genes and endogenous retroviruses in vertebrates.
Article
Biochemistry & Molecular Biology
Marie-Elisa Pinson, Franck Court, Aymeric Masson, Yoan Renaud, Allison Fantini, Ophelie Bacoeur-Ouzillou, Marie Barriere, Bruno Pereira, Pierre-Olivier Guichet, Emmanuel Chautard, Lucie Karayan-Tapon, Pierre Verrelle, Philippe Arnaud, Catherine Vaurs-Barriere
Summary: In addition to the consequences of retrotransposition, L1 retrotransposons affect the host genome through their antisense promoter. The study found widespread expression of LCT in normal brain and glioma samples, with the transcriptional activities of L1 antisense promoters and their host loci being coupled.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Elisa Le Boiteux, Pierre-Olivier Guichet, Konstantin Masliantsev, Bertille Montibus, Catherine Vaurs-Barriere, Celine Gonthier-Gueret, Emmanuel Chautard, Pierre Verrelle, Lucie Karayan-Tapon, Anne Fogli, Franck Court, Philippe Arnaud
Summary: The overexpression of long non-coding RNA HOXA-AS2 in Glioma Stem Cells (GSCs) contributes to their aggressiveness by promoting proliferation and modulating the inflammation pathway through the regulation of key transcription factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Mathilde Dura, Aurelie Teissandier, Melanie Armand, Joan Barau, Clementine Lapoujade, Pierre Fouchet, Lorraine Bonneville, Mathieu Schulz, Michael Weber, Laura G. Baudrin, Sonia Lameiras, Deborah Bourc'his
Summary: DNA methylation is crucial for spermatogenesis, and the sterility of DNA methyltransferase mutant mice demonstrates its role. In this study, we uncover the division of labor in establishing the methylation landscape of male germ cells and its functions in spermatogenesis. DNMT3C prevents retrotransposons from interfering with meiosis, while DNMT3A broadly methylates the genome (except DNMT3C-dependent retrotransposons) and regulates spermatogonial stem cell (SSC) plasticity. Single-cell RNA sequencing and chromatin profiling reveal that Dnmt3A mutant SSCs can only self-renew and lose the ability to differentiate due to spurious enhancer activation. These findings highlight the importance of DNA methylation in male fertility: the epigenetic programming of SSC commitment to differentiation and lifelong spermatogenesis supply.
Article
Multidisciplinary Sciences
Celine Jouffe, Benjamin D. Weger, Eva Martin, Florian Atger, Meltem Weger, Cedric Gobet, Divya Ramnath, Aline Charpagne, Delphine Morin-Rivron, Elizabeth E. Powell, Matthew J. Sweet, Mojgan Masoodi, N. Henriette Uhlenhaut, Frederic Gachon
Summary: Obesity and liver diseases disrupt the circadian clock regulated by BMAL1, which affects nutrient metabolism and storage. In liver fibrosis, the activity of BMAL1 is perturbed. Knockout mice lacking BMAL1 are prone to obesity but protected against insulin resistance, hepatic steatosis, inflammation, and fibrosis. The disruption of the growth hormone and sex hormone pathways plays a critical role in this protection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Genetics & Heredity
Dylane Detilleux, Yannick G. Spill, Delphine Balaramane, Michael Weber, Anais Flore Bardet
Summary: This study integrated a massive amount of genomic data to predict transcription factors driving aberrant DNA methylation in 13 cancer types, and validated the role of some transcription factors in breast cancer.
EPIGENETICS & CHROMATIN
(2022)
Article
Medicine, Research & Experimental
Riccardo Rigo, Rabie Chelbi, Julie Agopian, Sebastien Letard, Aurelien Griffon, Hussein Ghamlouch, Julien Vernerey, Vasileios Ladopoulos, Edwige Voisset, Paulo De Sepulveda, Geoffrey Guittard, Jacques A. Nunes, Ghislain Bidaut, Berthold Gottgens, Michael Weber, Olivier A. Bernard, Patrice Dubreuil, Erinn Soucie
Summary: Research suggests that mutation of TET2 is associated with various immune pathologies, particularly in mast cells. TET2 deficiency leads to hypermethylation of immune response gene regions, affecting gene expression and inflammation signals, ultimately resulting in immune tolerance and pathological inflammation.
Article
Cell Biology
Sebastien Calvet, Sephora Sallis, Nehme Saksouk, Cosette Rebouissou, Catherine Teyssier, Annick Lesne, Florence Cammas, Thierry Forne
Summary: About half of the mammalian genome is made up of repeated elements, and endogenous retroviruses (ERVs) are known to affect gene expression and cancer development. The HP1 protein has a crucial role in establishing and functioning heterochromatin, and its loss in hepatocytes results in the reactivation of specific ERVs and the development of liver tumors. This study discovered that certain HP1-dependent ERVs located upstream of genes Mbd1 and Trim24 can act as alternative promoters or potential enhancers, forming a loop with promoters of endogenous genes depending on the genomic context and HP1 expression level.
Article
Biochemistry & Molecular Biology
Hala Al Adhami, Judith Vallet, Celia Schaal, Paul Schumacher, Anais Flore Bardet, Michael Dumas, Johana Chicher, Philippe Hammann, Sylvain Daujat, Michael Weber
Summary: Many germline genes are epigenetically repressed in mammals to prevent inappropriate expression in somatic cells. Through studying chromatin signature and conducting a CRISPR-Cas9 knock-out screen, researchers discovered that germline gene repression depends on the polycomb complex PRC1.6 and DNA methylation in mouse embryonic stem cells. They also identified and characterized new genes, including Usp7, Shfm1, and Erh, that contribute to germline gene repression. These findings provide insights into the mechanisms and factors involved in silencing germline genes in embryonic stem cells.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Genetics & Heredity
Kim Philipp Jablonski, Leopold Carron, Julien Mozziconacci, Thierry Forne, Marc-Thorsten Huett, Annick Lesne
Summary: In this study, the researchers investigated the distribution of disease-associated single-nucleotide polymorphisms (SNPs) in relation to topologically associating domains (TADs) and their borders. They found that a fraction of diseases, especially cancers, showed a preferential localization of risk loci in these genomic regions. The results suggest that genetic variations affecting the genome partitioning within TADs may contribute to the genetic risk of certain diseases, particularly cancers.