A5053994131- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- Nuclear Structure and Function
- Genetics and Neurodevelopmental Disorders
- Advanced biosensing and bioanalysis techniques
- DNA Repair Mechanisms
The Netherlands Cancer Institute
2016-2025
Oncode Institute
2016-2020
Protein Research Foundation
2017-2019
Osaka University
2017-2019
Transcriptionally inactive genes are often positioned at the nuclear lamina (NL), as part of large lamina-associated domains (LADs). Activation such is accompanied by repositioning toward interior. How this process works and how it impacts flanking chromosomal regions poorly understood. We addressed these questions systematic activation or inactivation individual genes, followed detailed genome-wide analysis NL interactions, replication timing, transcription patterns. Gene inside LADs...
Abstract The dynamic three-dimensional (3D) organization of the human genome (the “4D Nucleome”) is closely linked to function. Here, we integrate a wide variety genomic data generated by 4D Nucleome Project provide detailed view 3D in widely used embryonic stem cells (H1-hESCs) and immortalized fibroblasts (HFFc6). We extensive benchmarking mapping assays these diverse datasets annotate spatial features across scales. reveal rich complexity chromatin domains their sub-nuclear positions,...
ABSTRACT DNA replication timing (RT) is correlated with transcription during cell fate changes but there are many exceptions and our understanding of this relationship suffers from a paucity reductionist approaches. Here, we manipulated length strength in hybrid-genome mouse embryonic stem cells (mESCs) at single locus upstream the silent, late replicating, Pleiotrophin (Ptn) gene, directly comparing RT to nascent rates engineered vs. wild-type alleles. First, inserted four reporter genes...
The chromatin remodeling complexes accessibility complex and ATP-utilizing assembly factor (ACF) combine the ATPase ISWI with signature subunit ACF1. These enzymes catalyze well-studied nucleosome sliding reactions in vitro, but how their actions affect physiological gene expression remains unclear. Here, we explored influence of Drosophila melanogaster complex/ACF on transcription by using complementary gain- loss-of-function approaches. Targeting ACF1 to multiple reporter genes inserted at...
DNA methylation controls gene expression, and once established, patterns are faithfully copied during replication by the maintenance methyltransferase Dnmt1. In vivo, Dnmt1 interacts with Uhrf1, which recognizes hemimethylated CpGs. Recently, we reported that Uhrf1-catalyzed K18- K23-ubiquitinated histone H3 binds to N-terminal region (the focus targeting sequence, RFTS) of stimulate its activity. However, it is not yet fully understood how ubiquitinated stimulates Here, show...
Chromatin proteins control gene activity in a concerted manner. We developed high-throughput assay to study the effects of local chromatin environment on regulatory protein interest. The combines previously reported multiplexing strategy based barcoded randomly integrated reporters with Gal4-mediated tethering. applied Drosophila heterochromatin 1a (HP1a), which is mostly known as repressive but has also been linked transcriptional activation. Recruitment over 1000 genomic locations revealed...
DNA methylation in promoter regions represses gene expression and is copied over mitotic divisions by Dnmt1. Dnmt1 activity regulated its replication foci targeting sequence ( RFTS ) domain which masks the catalytic pocket. It has been shown that on unmethylated inhibited nucleosome cores. In present study, we aimed to assess effect of nuclesome formation maintenance at single CpG resolution. We show fully methylates naked linker dinucleosomes, whereas was repressed all sites core particles....
Abstract It is largely unclear whether genes that are naturally embedded in lamina associated domains (LADs) inactive due to their chromatin environment, or LADs merely secondary the lack of transcription. We show hundreds human promoters become active when moved from native LAD position a neutral context same cells, indicating form repressive environment. Another set inside able "escape" repression, although transcription elongation attenuated. By inserting reporters into thousands genomic...
Abstract Transcriptionally inactive genes are often positioned at the nuclear lamina (NL), as part of large lamina-associated domains (LADs). Activation such is accompanied by repositioning towards interior. How this process works and how it impacts flanking chromosomal regions poorly understood. We addressed these questions systematic manipulation gene activity detailed analysis NL interactions. inside LADs typically causes detachment entire transcription unit but rarely more than 50-100 kb...
ABSTRACT The chromatin remodeling complexes CHRAC and ACF combine the ATPase ISWI with signature subunit ACF1. These enzymes catalyze well-studied nucleosome sliding reactions in vitro , but how their actions affect physiological gene expression is unclear. Here we explored influence of Drosophila CHRAC/ACF on transcription by complementary gain- loss-of-function approaches. Targeting ACF1 to multiple reporter genes inserted at many different genomic locations revealed a context-dependent...