A5080587435- Epigenetics and DNA Methylation
- Estrogen and related hormone effects
- Genomics and Chromatin Dynamics
- Computational Drug Discovery Methods
- Nutrition, Genetics, and Disease
- Bioinformatics and Genomic Networks
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
- interferon and immune responses
- Cancer-related molecular mechanisms research
- Developmental Biology and Gene Regulation
- RNA modifications and cancer
- Cancer Cells and Metastasis
- Congenital heart defects research
- Cancer-related gene regulation
- Pancreatic and Hepatic Oncology Research
- Chromosomal and Genetic Variations
- Molecular Biology Techniques and Applications
- Gene expression and cancer classification
- Gene Regulatory Network Analysis
- CRISPR and Genetic Engineering
- Histone Deacetylase Inhibitors Research
- Glioma Diagnosis and Treatment
Medical University of Vienna
2021-2025
Lawrence Berkeley National Laboratory
2016-2024
Comprehensive Cancer Center Vienna
2022-2024
Imperial College London
2018-2024
University of Vienna
2024
The London College
2018-2020
Hammersmith Hospital
2020
European Institute of Oncology
2010-2019
Abstract The human and mouse genomes contain instructions that specify RNAs proteins govern the timing, magnitude, cellular context of their production. To better delineate these elements, phase III Encyclopedia DNA Elements (ENCODE) Project has expanded analysis cell tissue repertoires RNA transcription, chromatin structure modification, methylation, looping, occupancy by transcription factors RNA-binding proteins. Here we summarize efforts, which have produced 5,992 new experimental...
Mammalian genomes are pervasively transcribed outside mapped protein-coding genes. One class of extragenic transcription products is represented by long non-coding RNAs (lncRNAs), some which result from Pol_II bona-fide RNA Whether all lncRNAs described insofar genes, however, still unclear. Here we have characterized sites located genes in a highly regulated response, macrophage activation endotoxin. Using chromatin signatures, could unambiguously classify binding as belonging to either...
Histone deacetylases (HDACs) regulate inflammatory gene expression, as indicated by the potent antiinflammatory activity of pan-HDAC inhibitors. However, specific contribution each 11 HDAC proteins to expression program is unknown. Using an integrated genomic approach, we found that Hdac3-deficient macrophages were unable activate almost half when stimulated with LPS. A large part activation defect was attributable loss basal and LPS-inducible IFN-β, which maintains Stat1 protein levels in...
The Encyclopedia of DNA Elements (ENCODE) project has established a genomic resource for mammalian development, profiling diverse panel mouse tissues at 8 developmental stages from 10.5 days after conception until birth, including transcriptomes, methylomes and chromatin states. Here we systematically examined the state accessibility in developing fetus. In total performed 1,128 immunoprecipitation with sequencing (ChIP-seq) assays histone modifications 132 assay transposase-accessible using...
Understanding how regulatory sequences interact in the context of chromosomal architecture is a central challenge biology. Chromosome conformation capture revealed that mammalian chromosomes possess rich hierarchy structural layers, from multi-megabase compartments to sub-megabase topologically associating domains (TADs) and sub-TAD contact domains. TADs appear act as microenvironments by constraining segregating interactions across discrete regions. However, it unclear whether other (or...
The Encylopedia of DNA Elements (ENCODE) Project launched in 2003 with the long-term goal developing a comprehensive map functional elements human genome. These included genes, biochemical regions associated gene regulation (for example, transcription factor binding sites, open chromatin, and histone marks) transcript isoforms. marks serve as sites for candidate cis-regulatory (cCREs) that may roles regulating expression1. project has been extended to model organisms, particularly mouse. In...
Topologically associating domain (TAD) boundaries partition the genome into distinct regulatory territories. Anecdotal evidence suggests that their disruption may interfere with normal gene expression and cause disease phenotypes1-3, but overall extent to which this occurs remains unknown. Here we demonstrate targeted deletions of TAD a range disruptions in vivo function organismal development. We used CRISPR editing mice individually delete eight (11-80 kb size) from genome. All examined...
Abstract Colorectal malignancies are a leading cause of cancer-related death 1 and have undergone extensive genomic study 2,3 . However, DNA mutations alone do not fully explain malignant transformation 4–7 Here we investigate the co-evolution genome epigenome colorectal tumours at single-clone resolution using spatial multi-omic profiling individual glands. We collected 1,370 samples from 30 primary cancers 8 concomitant adenomas generated 1,207 chromatin accessibility profiles, 527 whole...
Fibro-adipogenic progenitors (FAPs) are important components of the skeletal muscle regenerative environment. Whether FAPs support regeneration or promote fibro-adipogenic degeneration is emerging as a key determinant in pathogenesis muscular diseases, including Duchenne dystrophy (DMD). However, molecular mechanism that controls FAP lineage commitment and activity currently unknown. We show here an HDAC–myomiR–BAF60 variant network regulates fate dystrophic muscles mdx mice. Combinatorial...
Abstract Endocrine therapies target the activation of oestrogen receptor alpha (ERα) via distinct mechanisms, but it is not clear whether breast cancer cells can adapt to treatment using drug-specific mechanisms. Here we demonstrate that resistance emerges epigenetic reprogramming. Resistant display a spectrum phenotypical changes with invasive phenotypes evolving in lines resistant aromatase inhibitor (AI). Orthogonal genomics analysis reprogrammed regulatory regions identifies individual...
Resistant tumours are thought to arise from the action of Darwinian selection on genetically heterogenous cancer cell populations. However, simple clonal is inadequate describe late relapses often characterising luminal breast cancers treated with endocrine therapy (ET), suggesting a more complex interplay between genetic and non-genetic factors. Here, we dissect contributions diversity transcriptional plasticity during early phases ET at single-cell resolution. Using RNA-sequencing imaging...