8 results on '"Franka J. Rang"'
Search Results
2. Causes and Consequences of Age-Related Changes in DNA Methylation: A Role for ROS?
- Author
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Franka J. Rang and Johannes Boonstra
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DNA methylation ,methylcytosine ,aging ,reactive oxygen species ,mechanisms ,Biology (General) ,QH301-705.5 - Abstract
Recent genome-wide analysis of C-phosphate-G (CpG) sites has shown that the DNA methylome changes with increasing age, giving rise to genome-wide hypomethylation with site‑specific incidences of hypermethylation. This notion has received a lot of attention, as it potentially explains why aged organisms generally have a higher risk of age-related diseases. However, very little is known about the mechanisms that could cause the occurrence of these changes. Moreover, there does not appear to be a clear link between popular theories of aging and alterations in the methylome. Some of the most fruitful of these theories attribute an important role to reactive oxygen species, which seem to be responsible for an increase in oxidative damage to macromolecules, such as DNA, during the lifetime of an organism. In this review, the connection between changes in DNA methylation and these reactive oxygen species is discussed, as well as the effect of these changes on health. Deeper insights into the nature, causes and consequences of the aging methylome might provide a deeper understanding of the molecular mechanisms of aging and eventually contribute to the development of new diagnostic and therapeutic tools.
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- 2014
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3. H3K27me3 dictates atypical genome-nuclear lamina interactions and allelic asymmetry during early embryogenesis
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Isabel Guerreiro, Franka J. Rang, Yumiko K. Kawamura, Femke C. Groenveld, Ramada E. van Beek, Silke J. A. Lochs, Ellen Boele, Antoine H. M. F. Peters, and Jop Kind
- Abstract
The very first days of mammalian embryonic development are accompanied by epigenetic reprogramming and extensive changes in nuclear organization. In particular, genomic regions located at the periphery of the nucleus, termed lamina-associated domains (LADs), undergo major rearrangements after fertilization. However, the role of LADs in regulating gene expression as well as the interplay with various chromatin marks during preimplantation development remains elusive. In this study, we obtained single-cell LAD profiles coupled with the corresponding gene expression readout throughout the first days of mouse development. We detect extensive cell-cell LAD variability at the 2-cell stage, which surprisingly does not seem to functionally affect gene expression. This suggests an unusual uncoupling between 3D-nuclear genome organization and gene expression during totipotent developmental stages. By analyzing LAD dynamics and chromatin states across early developmental stages in an allelic-specific manner, we identify genomic regions that transiently detach from the nuclear lamina and are enriched by non-canonical H3K27me3. Upon maternal knock-out of a component of the Polycomb repressive complex 2 and concomitant loss of H3K27me3 during early embryogenesis, these regions relocate to the lamina at the 2-cell stage. Our results suggest that H3K27me3 is the prime determinant in establishing the atypical distribution of the genome at the nuclear periphery during the first days of embryonic development. This study provides insight into the molecular mechanisms regulating nuclear organization of parental genomes during very early mammalian development.
- Published
- 2023
4. The role of heterochromatin in 3D genome organization during preimplantation development
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Franka J. Rang, Jop Kind, and Isabel Guerreiro
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General Biochemistry, Genetics and Molecular Biology - Published
- 2023
5. Single-cell profiling of transcriptome and histone modifications with EpiDamID
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Christian Valdes-Quezada, Sandra S. de Vries, Yuko Sato, Franka J. Rang, Ellen Boele, Kim L. de Luca, Jeroen Bakkers, Jop Kind, Hiroshi Kimura, Phong D. Nguyen, and Isabel Guerreiro
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Transcriptome ,Histone ,Heterochromatin ,Gene regulatory network ,biology.protein ,Computational biology ,Epigenome ,Biology ,biology.organism_classification ,Zebrafish ,Genome ,Chromatin - Abstract
Recent advances in single-cell sequencing technologies have enabled simultaneous measurement of multiple cellular modalities, including various combinations of transcriptome, genome and epigenome. However, comprehensive profiling of the histone post-translational modifications that influence gene expression at single-cell resolution has remained limited. Here, we introduce EpiDamID, an experimental approach to target a diverse set of chromatin types by leveraging the binding specificities of genetically engineered proteins. By fusing Dam to single-chain variable fragment antibodies, engineered chromatin reader domains, or endogenous chromatin-binding proteins, we render the DamID technology and all its implementations compatible with the genome-wide identification of histone post-translational modifications. Importantly, this enables the joint analysis of chromatin marks and transcriptome in a variety of biological systems at the single-cell level. In this study, we use EpiDamID to profile single-cell Polycomb occupancy in mouse embryoid bodies and provide evidence for hierarchical gene regulatory networks. We further demonstrate the applicability of this method to in vivo systems by mapping H3K9me3 in early zebrafish embryogenesis, and detect striking heterochromatic regions specifically in the notochord. Overall, EpiDamID is a new addition to a vast existing toolbox for obtaining systematic insights into the role of chromatin states during dynamic cellular processes.
- Published
- 2021
6. Simultaneous quantification of protein-DNA interactions and transcriptomes in single cells with scDamT-seq
- Author
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Siddharth S. Dey, Sandra S. de Vries, Dylan Mooijman, Kim L. de Luca, Franka J. Rang, Jop Kind, Alex Chialastri, Koos Rooijers, Silke J A Lochs, Corina M. Markodimitraki, and Hubrecht Institute for Developmental Biology and Stem Cell Research
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Site-Specific DNA-Methyltransferase (Adenine-Specific) ,Sequence analysis ,Recombinant Fusion Proteins ,Computational biology ,DNA/genetics ,General Biochemistry, Genetics and Molecular Biology ,Article ,Cell Line ,Transcriptome ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Transcription (biology) ,Cell Line, Tumor ,Gene expression ,Escherichia coli ,Animals ,Humans ,030304 developmental biology ,Recombinant Fusion Proteins/genetics ,0303 health sciences ,Tumor ,Chemistry ,Escherichia coli Proteins ,Gene Expression Profiling ,Single-Cell Analysis/methods ,Proteins ,DNA ,Genomics ,Sequence Analysis, DNA ,DNA Methylation ,Fusion protein ,Chromatin ,Genomics/methods ,DNA/methods ,Escherichia coli/genetics ,Sequence Analysis, DNA/methods ,DNA methylation ,Proteins/genetics ,Site-Specific DNA-Methyltransferase (Adenine-Specific)/genetics ,Gene Expression Profiling/methods ,Single-Cell Analysis ,Escherichia coli Proteins/genetics ,Sequence Analysis ,030217 neurology & neurosurgery ,Protein Binding - Abstract
Protein-DNA interactions are essential for establishing cell type-specific chromatin architecture and gene expression. We recently developed scDam&T-seq, a multi-omics method that can simultaneously quantify protein-DNA interactions and the transcriptome in single cells. The method effectively combines two existing methods: DNA adenine methyltransferase identification (DamID) and CEL-Seq2. DamID works through the tethering of a protein of interest (POI) to the Escherichia coli DNA adenine methyltransferase (Dam). Upon expression of this fusion protein, DNA in proximity to the POI is methylated by Dam and can be selectively digested and amplified. CEL-Seq2, in contrast, makes use of poly-dT primers to reverse transcribe mRNA, followed by linear amplification through in vitro transcription. scDam&T-seq is the first technique capable of providing a combined readout of protein-DNA contact and transcription from single-cell samples. Once suitable cell lines have been established, the protocol can be completed in 5 d, with a throughput of hundreds to thousands of cells. The processing of raw sequencing data takes an additional 1-2 d. Our method can be used to understand the transcriptional changes a cell undergoes upon the DNA binding of a POI. It can be performed in any laboratory with access to FACS, robotic and high-throughput-sequencing facilities.
- Published
- 2019
7. Simultaneous quantification of protein-DNA contacts and transcriptomes in single cells
- Author
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Sandra S. de Vries, Koos Rooijers, Franka J. Rang, Siddharth S. Dey, Corina M. Markodimitraki, Kim L. de Luca, Alex Chialastri, Jop Kind, Dylan Mooijman, and Hubrecht Institute for Developmental Biology and Stem Cell Research
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Cell type ,Methyltransferase ,In silico ,Cell ,Biomedical Engineering ,Bioengineering ,Computational biology ,Biology ,Applied Microbiology and Biotechnology ,Article ,Cell Line ,Transcriptome ,chemistry.chemical_compound ,03 medical and health sciences ,0302 clinical medicine ,Gene expression ,medicine ,Animals ,Transcription factor ,030304 developmental biology ,Genomic organization ,Regulation of gene expression ,0303 health sciences ,DNA-Binding Proteins/metabolism ,Single-Cell Analysis/methods ,Epigenome ,Embryonic stem cell ,Cell biology ,Chromatin ,DNA-Binding Proteins ,medicine.anatomical_structure ,Gene Expression Regulation ,chemistry ,Molecular Medicine ,Single-Cell Analysis ,DNA ,030217 neurology & neurosurgery ,Protein Binding ,Biotechnology - Abstract
The epigenome plays a critical role in regulating gene expression in mammalian cells. However, understanding how cell-to-cell heterogeneity in the epigenome influences gene expression variability remains a major challenge. Here we report a novel method for simultaneous single-cell quantification of protein-DNA contacts with DamID and transcriptomics (scDamID&T). This method enables quantifying the impact of protein-DNA contacts on gene expression from the same cell. By profiling lamina-associated domains (LADs) in human cells, we reveal different dependencies between genome-nuclear lamina (NL) association and gene expression in single cells. In addition, we introduce the E. coli methyltransferase, Dam, as an in vivo marker of chromatin accessibility in single cells and show that scDamID&T can be utilized as a general technology to identify cell types in silico while simultaneously determining the underlying gene-regulatory landscape. With this strategy the effect of chromatin states, transcription factor binding, and genome organization on the acquisition of cell-type specific transcriptional programs can be quantified.
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- 2019
- Full Text
- View/download PDF
8. From squiggle to basepair: computational approaches for improving nanopore sequencing read accuracy
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Jeroen de Ridder, Franka J. Rang, and Wigard P. Kloosterman
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0301 basic medicine ,lcsh:QH426-470 ,Sequencing data ,Word error rate ,Review ,Biology ,03 medical and health sciences ,Nanopores ,Escherichia coli ,Humans ,lcsh:QH301-705.5 ,Base Pairing ,Genome ,High-Throughput Nucleotide Sequencing ,DNA ,Sequence Analysis, DNA ,Markov Chains ,lcsh:Genetics ,Nanopore ,Klebsiella pneumoniae ,030104 developmental biology ,lcsh:Biology (General) ,Computer engineering ,Nanopore sequencing ,Neural Networks, Computer ,Artifacts - Abstract
Nanopore sequencing is a rapidly maturing technology delivering long reads in real time on a portable instrument at low cost. Not surprisingly, the community has rapidly taken up this new way of sequencing and has used it successfully for a variety of research applications. A major limitation of nanopore sequencing is its high error rate, which despite recent improvements to the nanopore chemistry and computational tools still ranges between 5% and 15%. Here, we review computational approaches determining the nanopore sequencing error rate. Furthermore, we outline strategies for translation of raw sequencing data into base calls for detection of base modifications and for obtaining consensus sequences. Electronic supplementary material The online version of this article (10.1186/s13059-018-1462-9) contains supplementary material, which is available to authorized users.
- Published
- 2018
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