A5076749126- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- bioluminescence and chemiluminescence research
- Pluripotent Stem Cells Research
- 3D Printing in Biomedical Research
- Cancer Genomics and Diagnostics
- Electrochemical Analysis and Applications
- DNA Repair Mechanisms
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- Histone Deacetylase Inhibitors Research
- Viral Infectious Diseases and Gene Expression in Insects
- Electrochemical sensors and biosensors
- Single-cell and spatial transcriptomics
- Neuroscience and Neural Engineering
- Cancer Cells and Metastasis
- RNA Research and Splicing
- Molecular Communication and Nanonetworks
- Biosensors and Analytical Detection
- Force Microscopy Techniques and Applications
- Advanced Chemical Sensor Technologies
- RNA Interference and Gene Delivery
- Bacterial biofilms and quorum sensing
- Analytical Chemistry and Sensors
Novo Nordisk Foundation
2022-2025
University of Copenhagen
2022-2025
Hebrew University of Jerusalem
2011-2021
Edmond and Lily Safra Children's Hospital
2016
Tumors comprise functionally diverse subpopulations of cells with distinct proliferative potential. Here, we show that dynamic epigenetic states defined by the linker histone H1.0 determine which within a tumor can sustain long-term cancer growth. Numerous types exhibit high inter- and intratumor heterogeneity H1.0, levels correlating differentiation status, patient survival, and, at single-cell level, stem cell markers. Silencing promotes maintenance self-renewing inducing derepression...
Modified parental histones are segregated symmetrically to daughter DNA strands during replication and can be inherited through mitosis. How this may sustain the epigenome cell identity remains unknown. Here we show that transmission of histone-based information maintains fidelity embryonic stem plasticity. Asymmetric segregation H3-H4 in MCM2-2A mutants compromised mitotic inheritance histone modifications globally altered epigenome. This included widespread spurious deposition repressive...
Embryonic stem cells (ESCs) exhibit unique chromatin features, including a permissive transcriptional program and an open, decondensed state. Induced pluripotent (iPSCs), which are very similar to ESCs, hold great promise for therapy basic research. However, the mechanisms by reprogramming occurs organization that underlies process largely unknown. Here we characterize compare epigenetic landscapes of partially fully reprogrammed iPSCs mouse embryonic fibroblasts (MEFs) serves as standard...
During every cell cycle, both the genome and associated chromatin must be accurately replicated. Chromatin Assembly Factor-1 (CAF-1) is a key regulator of replication, but how CAF-1 functions in relation to DNA replication machinery unknown. Here, we reveal that this crosstalk differs between leading lagging strand at forks. Using biochemical reconstitutions, show histones promote recruitment its binding partner PCNA two complexes are required for efficient nucleosome assembly under these...
We present replication-aware single-molecule accessibility mapping (RASAM), a method to nondestructively measure replication status and protein-DNA interactions on chromatin genome-wide. Using RASAM, we uncover genome-wide state of "hyperaccessibility" post-replication that resolves over several hours. Combining RASAM with cellular models for rapid protein degradation, demonstrate histone chaperone CAF-1 reduces nascent by filling single-molecular "gaps" generating closely spaced...
The pluripotent genome is characterized by unique epigenetic features and a decondensed chromatin conformation. However, the relationship between regulation pluripotency not altogether clear. Here, using an enhanced MEF/ESC fusion protocol, we compared reprogramming potency histone modifications of different embryonic stem cell (ESC) lines (R1, J1, E14, C57BL/6) found that E14 ESCs are significantly less potent, with reduced H3K9ac levels. Treatment deacetylase (HDAC) inhibitors (HDACi)...
In BriefAlajem et al. develop an assay that indicates differential association of SMARCD1 with chromatin in embryonic stem cells (ESCs) and earlydifferentiating cells.SMARCD1 is associated bivalent genes ESCs, regulates H3K4me3/H3K27me3 distribution, binds the pluripotency factor Klf4.
Neuronal stimulation leads to immediate early gene (IEG) expression through calcium-dependent mechanisms. In recent years, considerable attention has been devoted the transcriptional responses after neuronal stimulation, but relatively little is known about changes in chromatin dynamics that follow activation. Here, we use fluorescence recovery photobleaching, biochemical fractionations, and immunoprecipitation show KCl-induced depolarization primary cultured cortical neurons causes a rapid...
Tumor-initiating cells are a subpopulation of that have self-renewal capacity to regenerate tumor. Here, we identify stem cell-like chromatin features in human glioblastoma initiating (GICs) and link them loss the repressive histone H3 lysine 9 trimethylation (H3K9me3) mark. Increasing H3K9me3 levels by demethylase inhibition led cell death GICs but not their differentiated counterparts. The induction apoptosis was accompanied activating acetylation (H3K9ac) modification accumulation DNA...
In the process of DNA replication, first steps in restoring chromatin landscape involve parental histone recycling and new deposition. Disrupting to either leading or lagging strand induces asymmetric inheritance, affecting epigenome maintenance cellular identity. However, order kinetics these effects remain elusive. Here, we use inducible mutants dissect early late consequences impaired recycling. Simultaneous disruption both (POLE4) (MCM2-2A) pathways impairs transmission histones newly...
Embryonic stem cells (ESCs) are regulated by pluripotency-related transcription factors in concert with chromatin regulators. To identify additional cell regulators, we screened a library of endogenously labeled fluorescent fusion proteins mouse ESCs for fluorescence loss during differentiation. We identified SET, which displayed rapid isoform shift early differentiation from the predominant ESCs, SETα, to primary differentiated cells, SETβ, through alternative promoters. SETα is selectively...
Long-term perturbation of de novo chromatin assembly during DNA replication has profound effects on epigenome maintenance and cell fate. The early mechanistic origin these defects is unknown. Here, we combine acute degradation factor 1 (CAF-1), a key player in assembly, with single-cell genomics, quantitative proteomics, live microscopy to uncover initiating mechanisms human cells. CAF-1 loss immediately slows down speed renders nascent hyper-accessible. A rapid cellular response, distinct...
Abstract Upon DNA breakage, a genomic locus undergoes alterations in 3-D chromatin architecture to facilitate signaling and repair. While cells possess mechanisms repair damaged DNA, it is unknown whether the surrounding restored its naïve state. We show that single double-strand break (DSB) within topologically-associated domain (TAD) harboring conformation-sensitive genes causes lasting alterations, which persist after completion of feature structural changes, compaction loss local RNA...