Article
Cell Biology
Wei Yang, Junjun Cao, David G. McVey, Shu Ye
Summary: Genome-wide association studies have identified a link between the genetic variant rs17514846 in the FURIN gene and coronary artery disease. Our study demonstrates that rs17514846 modulates FURIN expression through DNA methylation inhibition, which is mediated by the MeCP2 protein. Knockdown of MeCP2 increases FURIN expression, affecting monocyte migration and proliferation.
Review
Oncology
Kazem Nejati-Koshki, Chris-Tiann Roberts, Ghader Babaei, Mojgan Rastegar
Summary: Epigenetic mechanisms control gene expression and cellular identity, with DNA methylation being an important epigenetic modification. Methyl-CpG-Binding Protein 2 (MeCP2) is a reader of DNA methylation and plays key roles in cellular identity and function. Recent studies have uncovered MeCP2's involvement in tumorigenesis of various human cancers, highlighting its potential oncogenic properties. This article provides an overview of the emerging role of MeCP2 as an oncogene in different types of human cancer.
Article
Biochemistry & Molecular Biology
Aaron John Stevens, Lucy de Jong, Martin Alexander Kennedy
Summary: DNA modifications, such as methylation, may act as a dynamic switch to promote or alleviate the formation of G-quadruplex structures. The interaction between epigenetic DNA modifications, G4 formation, and the 3D architecture of the genome is a complex and developing area of research. Such interactions could represent novel mechanisms for important biological functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Deivid C. Rodrigues, Marat Mufteev, Kyoko E. Yuki, Ashrut Narula, Wei Wei, Alina Piekna, Jiajie Liu, Peter Pasceri, Olivia S. Rissland, Michael D. Wilson, James Ellis
Summary: This study measured transcription rate and mRNA half-life changes in RTT patient-derived neurons and reinterpreted nuclear and whole-cell RNAseq from Mecp2 mice. The results showed that dysregulation of genes in RTT is caused by changes in transcription rate or half-life, but genes are buffered when both change. In addition, three dinucleotide frequencies were found to be better predictors of transcription rate changes than CA and CG. MicroRNA and RNA-binding Protein (RBP) motifs were enriched in the 3'UTRs of genes with half-life changes, while nuclear RBP motifs were enriched in buffered genes with increased transcription rate. The study revealed post-transcriptional mechanisms in neurodevelopmental disorders caused by mutations in transcriptional modulator genes.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Qi Chen, Hao Li, Yusi Liu, Min Zhao
Summary: This study comprehensively analyzed the epigenetic regulation in rheumatoid arthritis (RA) using differential analysis and cross-analysis. The results identified differentially methylated sites, differentially expressed genes, and differentially expressed miRNAs associated with RA. A comprehensive epigenetic regulatory network was constructed, and core regulatory genes were identified. This study provides a new direction for future research on the epigenetic mechanisms of RA.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Marjorie Buist, David Fuss, Mojgan Rastegar
Summary: The study analyzed the transcriptional effects of metformin on MECP2E1/E2-BDNF and found that metformin can post-transcriptionally induce BDNF and/or MECP2E1 while inhibiting MECP2E2 transcriptionally. On the other hand, simvastatin significantly inhibited BDNF transcription without affecting MECP2E2 transcripts significantly. The impact of serum starvation on the transcriptional regulation of MECP2E1 by simvastatin was only detected in non-serum starved cells.
Article
Cell Biology
Vijay Swahari, Ayumi Nakamura, Emilie Hollville, Hume Stroud, Jeremy M. Simon, Travis S. Ptacek, Matthew Beck, Cornelius Flowers, Jiami Guo, Charlotte Plestant, Jie Liang, C. Lisa Kurtz, Matt Kanke, Scott M. Hammond, You-Wen He, E. S. Anton, Praveen Sethupathy, Sheryl S. Moy, Michael E. Greenberg, Mohanish Deshmukh
Summary: The miR-29 family is significantly induced during the late stages of brain maturation, and plays a crucial role in restricting CH methylation in the brain through targeting of Dnmt3a. Deletion of miR-29 results in neurological deficits, premature lethality, and increased DNMT3A expression, highlighting the importance of CH methylation regulation for normal brain maturation.
Article
Biochemistry & Molecular Biology
Stefan Kunert, Verena Linhard, Sara Weirich, Michel Choudalakis, Florian Osswald, Lisa Kraemer, Anja R. Koehler, Alexander Broehm, Jan Wollenhaupt, Harald Schwalbe, Albert Jeltsch
Summary: The highly expressed DNMT3A DNA methyltransferase and MECP2 methylation reader in neurons interact through their DNMT3A-ADD and MECP2-TRD domains, and the interaction between MECP2 regulates the activity and subnuclear localization of DNMT3A. The interface of these two domains was mapped, revealing that the ADD domain interacts with the TRD domain through the D529-D531 region, while the TRD domain interacts with the ADD domain through residues 214-228, including K219 and K223. The mutations at the ADD-TRD interface disrupt the cellular interaction of these proteins in NIH3T3 cells.
Article
Biochemistry & Molecular Biology
Teresa Improda, Valentina Morgera, Maria Vitale, Lorenzo Chiariotti, Fabiana Passaro, Antonia Feola, Antonio Porcellini, Mariella Cuomo, Antonio Pezone
Summary: Cell identity is determined by chromatin structure and gene expression profiles, which rely on chromatin accessibility and DNA methylation. These epigenetic modifications are crucial for mammalian development and cellular identity. Dynamic DNA methylation and demethylation occur during cell fate commitment and terminal differentiation. By analyzing the methylation configurations of gene promoters during murine brain differentiation, we found significant methyl-CpG profiles associated with gene silencing or activation. Interestingly, these methylation patterns mark different brain areas and cell types during differentiation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Samuel N. Bogan, Marie E. Strader, Gretchen E. Hofmann
Summary: This study investigates the effects of DNA methylation on gene expression and splicing in the larvae of the purple sea urchin. It finds that differential gene body methylation has stronger effects on gene expression among genes with poorly accessible transcriptional start sites, and the baseline transcript abundance influences the direction of this effect. Considering the interactions between methylation and chromatin accessibility, the transcriptional responses to maternal conditioning are significantly increased, suggesting that the relationship between methylation and gene regulation is partially explained by chromatin state.
Article
Oncology
Qinfeng Zhou, Yu Tian, Chenlu Xu, Juling Wang, Yongtang Jin
Summary: This study found that early-life exposure to traffic air pollution can lead to abnormal social behavior and protein expression, particularly more pronounced in male offspring with postnatal exposure.
CLINICAL EPIGENETICS
(2021)
Article
Biochemistry & Molecular Biology
Fernanda Wisnieski, Jaqueline Cruz Geraldis, Leonardo Caires Santos, Mariana Ferreira Leal, Danielle Queiroz Calcagno, Carolina Oliveira Gigek, Elizabeth Suchi Chen, Ana Carolina Anauate, Ricardo Artigiani, Samia Demachki, Paulo Pimentel Assumpcao, Laercio Gomes Lourenco, Carlos Haruo Arasaki, Julie Krainer, Stephan Pabinger, Rommel Rodriguez Burbano, Marilia Arruda Cardoso Smith
Summary: In this study, the research group identified a list of 83 genes potentially modulated by DNA methylation in GC cell lines, with LRRC37A2 playing a role in undifferentiated and poorly differentiated tumors. The study showed that reduced LRRC37A2 mRNA levels and increased LRRC37A2 exon methylation are associated with GC progression, emphasizing the potential utility of gene-related stratification for epigenetic therapy in GC patients.
Article
Cell & Tissue Engineering
Xi-Biao He, Fang Guo, Kexuan Li, Jiaqing Yan, Sang-Hun Lee
Summary: This study reveals the crucial role of MeCP2 in the specification of midbrain dopamine phenotype in mice, and demonstrates that the timing of MeCP2 expression affects the determination of dopamine phenotype in neural precursor cells (NPCs). Through analysis of DNA methylation dynamics, the study uncovers that Th gene expression is regulated by TET1-mediated demethylation. These findings highlight the significance of MeCP2 expression timing as a novel determining factor for guiding NPCs into the dopamine lineage.
Article
Biochemistry & Molecular Biology
Jiao Wang, Yushuo Xiao, Chengyu Liu, Yixue Huang, Robert B. Petersen, Ling Zheng, Kun Huang
Summary: MeCP2 plays a crucial role in both neurological and non-neurological disorders, including causing Rett syndrome in the former and cardiac dysfunction, liver injury, respiratory disorders, and other conditions in the latter. Research suggests that MeCP2 can influence various physiological and pathological processes in a DNA methylation-dependent or independent manner.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Review
Biochemistry & Molecular Biology
Xiancan Wang, Xianghai Kong, Xin Feng, Ding-Sheng Jiang
Summary: Ferroptosis is a type of programmed cell death characterized by increased levels of ferrous ions and lipid peroxidation. It has been found to play a role in various organ injuries and degenerative diseases, while insufficient ferroptosis has been linked to tumorigenesis. The regulatory mechanisms of ferroptosis involve iron metabolism, redox systems, and epigenetic mechanisms. This review provides a critical analysis of the molecular mechanisms and regulatory networks of ferroptosis, with a focus on the role of DNA, RNA, and protein methylation. The unanswered questions and debated findings in this field are also discussed.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Biochemical Research Methods
Martin Carballo-Pacheco, Michael D. Nicholson, Elin E. Lilja, Rosalind J. Allen, Bartlomiej Waclaw
PLOS COMPUTATIONAL BIOLOGY
(2020)
Article
Biology
Suman G. Das, Susana O. L. Direito, Bartlomiej Waclaw, Rosalind J. Allen, Joachim Krug
Article
Microbiology
Nikola Ojkic, Elin Lilja, Susana Direito, Angela Dawson, Rosalind J. Allen, Bartlomiej Waclaw
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2020)
Article
Biology
Cristina Parigini, Philip Greulich
Article
Genetics & Heredity
Kashyap Chhatbar, Justyna Cholewa-Waclaw, Ruth Shah, Adrian Bird, Guido Sanguinetti
Article
Biochemistry & Molecular Biology
Raphael Pantier, Kashyap Chhatbar, Timo Quante, Konstantina Skourti-Stathaki, Justyna Cholewa-Waclaw, Grace Alston, Beatrice Alexander-Howden, Heng Yang Lee, Atlanta G. Cook, Cornelia G. Spruijt, Michiel Vermeulen, Jim Selfridge, Adrian Bird
Summary: This study identified SALL4 as a protein that interprets base composition by binding to AT-rich motifs, affecting genome occupancy and genes regulation. Loss of pluripotency is triggered by downregulation of SALL4, leading to de-repression of a set of AT-rich genes promoting neuronal differentiation. Deletion of two other zinc-finger clusters had no phenotypic effect, indicating the importance of SALL4 in controlling cell fate.
Article
Biochemistry & Molecular Biology
Rebekah Tillotson, Justyna Cholewa-Waclaw, Kashyap Chhatbar, John C. Connelly, Sophie A. Kirschner, Shaun Webb, Martha V. Koerner, Jim Selfridge, David A. Kelly, Dina De Sousa, Kyla Brown, Matthew J. Lyst, Skirmantas Kriaucionis, Adrian Bird
Summary: The interaction of MeCP2 with sites of non-CG methylation, particularly mCAC, is crucial for normal brain function and may be related to the pathogenesis of Rett syndrome. Dysregulated genes in Mecp2 null and domain-swap mice are associated with other neurological disorders, suggesting potential targets for the Rett syndrome phenotype.
Article
Developmental Biology
Philip Greulich, Ben D. MacArthur, Cristina Parigini, Ruben J. Sanchez-Garcia
Summary: The arrangement of cells in tissues forms a lineage hierarchy to regulate tissue turnover. Based on the relationship between cell molecular 'states' and cell 'types', a self-renewing cell type is shown to only reside at the top of the lineage hierarchy in dynamic equilibrium. The property of 'stemness' is entirely determined by the cell environment, supporting the idea that stem cell identities are contextual.
Article
Biochemistry & Molecular Biology
Gordin Zupkovitz, Julijan Kabiljo, Michael Kothmayer, Katharina Schlick, Christian Schoefer, Sabine Lagger, Oliver Pusch
Summary: Erosion of the epigenetic DNA methylation landscape is a recognized hallmark of aging, and advances in high throughput sequencing techniques and DNA methylation data analysis have facilitated the establishment of accurate age prediction tools. The identification of key players in the DNA methylation machinery in the short-lived teleost aging model Nothobranchius furzeri and the comprehensive spatio-temporal expression profile of methylation-associated enzymes has been reported.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Geriatrics & Gerontology
Maria Butylina, Ursula Foeger-Samwald, Sonja Gamsjaeger, Katharina Wahl-Figlash, Michael Kothmayer, Eleftherios P. Paschalis, Oliver Pusch, Peter Pietschmann
Summary: This study investigates the bone properties of Nothobranchius furzeri, a potential model for age-related osteoporosis. The results show gender differences in bone structure and remodeling, as well as the impact of age on bone properties.
Article
Biochemistry & Molecular Biology
I. Garces de los Fayos Alonso, L. Zujo, I Wiest, P. Kodajova, G. Timelthaler, S. Edtmayer, M. Zrimsek, S. Kollmann, C. Giordano, M. Kothmayer, H. A. Neubauer, S. Dey, M. Schlederer, B. S. Schmalzbauer, T. Limberger, C. Probst, O. Pusch, S. Hogler, S. Tangermann, O. Merkel, A. Schiefer, C. Kornauth, N. Prutsch, M. Zimmerman, B. Abraham, J. Anagnostopoulos, L. Quintanilla-Martinez, S. Mathas, P. Wolf, D. Stoiber, P. B. Staber, G. Egger, W. Klapper, W. Woessmann, T. A. Look, P. Gunning, S. D. Turner, R. Moriggl, S. Lagger, L. Kenner
Summary: This study reveals the important role of PDGFRβ in aggressive ALCL and its activation of STAT5 in inducing cell growth and survival-related gene expression. Simultaneous deletion of STAT5 gene products significantly impairs cell viability. Additionally, blockade of PDGFRβ and STAT3/5 activity effectively obstructs tumor development. Thus, PDGFRβ and PDGFRβ-STAT3/5 signaling may serve as novel targets for the treatment of aggressive ALCL.
Article
Biology
Kashyap Chhatbar, John Connelly, Shaun Webb, Skirmantas Kriaucionis, Adrian Bird
Summary: The study found that CA repeats are not key mediators of MeCP2 function and there is no evidence to suggest that MeCP2 preferentially binds to CA repeat regions. Instead, CA repeat regions show typical CAC methylation levels similar to the surrounding genome and contribute modestly to MeCP2-mediated modulation of gene expression in accordance with their content of this canonical target motif.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biology
James A. Watson, Raphael Pantier, Uma Jayachandran, Kashyap Chhatbar, Beatrice Alexander-Howden, Valdeko Kruusvee, Michal Prendecki, Adrian Bird, Atlanta G. Cook
Summary: SALL4 maintains stem cell identity and is required for organ development. It interacts with the NuRD complex and recognizes AT-rich sequences through zinc fingers at the C-terminus. Missense mutations within the zinc fingers affect DNA binding and association with AT-rich genomic sites.
LIFE SCIENCE ALLIANCE
(2023)
Article
Cell Biology
Liam Barry-Carroll, Philip Greulich, Abigail R. Marshall, Kristoffer Riecken, Boris Fehse, Katharine E. Askew, Kaizhen Li, Olga Garaschuk, David A. Menassa, Diego Gomez-Nicola
Summary: Microglia are derived from the yolk sac and migrate into the brain during early embryonic development. They undergo in situ proliferation and ultimately colonize the entire brain by the third postnatal week in mice. This study reveals that their colonization is facilitated by clonal expansion of highly proliferative microglial progenitors distributed throughout the brain. Additionally, the spatial distribution of microglia changes from clustered to random during development.
Review
Cell & Tissue Engineering
Philip Greulich
Summary: This article gives an overview of quantitative modelling approaches in biology and provides guidance on how to use them in stem cell research. It points out that while quantitative modelling can boost biological research, careful considerations need to be taken to avoid pitfalls and understand its limitations.
CURRENT STEM CELL REPORTS
(2023)