A5056137343- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- Cancer-related molecular mechanisms research
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- DNA Repair Mechanisms
- Genetics and Neurodevelopmental Disorders
- Single-cell and spatial transcriptomics
- Studies on Chitinases and Chitosanases
- Animal Genetics and Reproduction
- Genetic Mapping and Diversity in Plants and Animals
- T-cell and B-cell Immunology
- Genomic variations and chromosomal abnormalities
- Cancer, Hypoxia, and Metabolism
- Reproductive Biology and Fertility
- Evolution and Genetic Dynamics
- Immune Cell Function and Interaction
- Developmental Biology and Gene Regulation
German Cancer Research Center
2018-2025
Heidelberg University
2018-2025
Cancer Research UK
2015-2024
University of Cambridge
2015-2024
Technical University of Munich
2024
DKFZ-ZMBH Alliance
2020-2023
University of Wisconsin–Madison
2021
Wellcome Sanger Institute
2011-2019
Cancer Research UK Cambridge Center
2007-2019
European Bioinformatics Institute
2014
We have determined how most of the transcriptional regulators encoded in eukaryote Saccharomyces cerevisiae associate with genes across genome living cells. Just as maps metabolic networks describe potential pathways that may be used by a cell to accomplish processes, this network regulator-gene interactions describes yeast cells can use regulate global gene expression programs. information identify motifs, simplest units architecture, and demonstrate an automated process motifs assemble...
The transcriptional regulatory networks that specify and maintain human tissue diversity are largely uncharted. To gain insight into this circuitry, we used chromatin immunoprecipitation combined with promoter microarrays to identify systematically the genes occupied by regulators HNF1alpha, HNF4alpha, HNF6, together RNA polymerase II, in liver pancreatic islets. We identified tissue-specific circuits formed HNF6 other transcription factors, revealing how these factors function as master of...
Whence Species Variation? Vertebrates have widely varying phenotypes that are at odds with their much more limited proteincoding genotypes and conserved messenger RNA expression patterns. Genes multiple exons introns can undergo alternative splicing, potentially resulting in protein isoforms (see the Perspective by Papasaikas Valcárcel ). Barbosa-Morais et al. (p. 1587 ) Merkin 1593 analyzed splicing across genomes of a variety vertebrates, including human, primates, rodents, opossum,...
Hormones and nutrients often induce genetic programs via signaling pathways that interface with gene-specific activators. Activation of the cAMP pathway, for example, stimulates cellular gene expression by means PKA-mediated phosphorylation cAMP-response element binding protein (CREB) at Ser-133. Here, we use genome-wide approaches to characterize target genes are regulated CREB in different contexts. was found occupy ≈4,000 promoter sites vivo , depending on presence methylation state...
The NOTCH1 signaling pathway directly links extracellular signals with transcriptional responses in the cell nucleus and plays a critical role during T development pathogenesis over 50% of human lymphoblastic leukemia (T-ALL) cases. However, little is known about programs activated by NOTCH1. Using an integrative systems biology approach we show that controls feed-forward-loop network promotes growth. Inhibition T-ALL cells led to reduction size elicited gene expression signature dominated...
The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding regulatory evolution mammals. Here, track promoters and enhancers active liver across 20 species from six diverse orders by profiling genomic enrichment H3K27 acetylation H3K4 trimethylation. We report that is universal feature genomes. Most recently evolved arise ancestral DNA exaptation, rather than lineage-specific expansions repeat elements. In...
Gorillas are humans' closest living relatives after chimpanzees, and of comparable importance for the study human origins evolution. Here we present assembly analysis a genome sequence western lowland gorilla, compare whole genomes all extant great ape genera. We propose synthesis genetic fossil evidence consistent with placing human–chimpanzee human–chimpanzee–gorilla speciation events at approximately 6 10 million years ago. In 30% genome, gorilla is closer to or chimpanzee than latter...
Transcription factors (TFs) direct gene expression by binding to DNA regulatory regions. To explore the evolution of regulation, we used chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) determine experimentally genome-wide occupancy two TFs, CCAAT/enhancer-binding protein alpha and hepatocyte nuclear factor 4 alpha, in livers five vertebrates. Although each TF displays highly conserved preferences, most is species-specific, aligned events present all species are rare....
Topological domains are key architectural building blocks of chromosomes, but their functional importance and evolutionary dynamics not well defined. We performed comparative high-throughput chromosome conformation capture (Hi-C) in four mammals characterized the conservation divergence chromosomal contact insulation resulting domain architectures within distantly related genomes. show that modular organization chromosomes is robustly conserved syntenic regions this compatible with binding...
CTCF-binding locations represent regulatory sequences that are highly constrained over the course of evolution. To gain insight into how these DNA elements conserved and spread through genome, we defined full spectrum sites, including a 33/34-mer motif, identified five thousand conserved, robust, tissue-independent by comparing ChIP-seq data from six mammals. Our indicate activation retroelements has produced species-specific expansions CTCF binding in rodents, dogs, opossum, which often...
Abstract Mutations in the cytosine‐5 RNA methyltransferase NSun2 cause microcephaly and other neurological abnormalities mice human. How post‐transcriptional methylation contributes to human disease is currently unknown. By comparing gene expression data with global methylomes patient fibroblasts NSun2‐deficient mice, we find that loss of increases angiogenin‐mediated endonucleolytic cleavage transfer RNAs ( tRNA ) leading an accumulation 5′ ‐derived small fragments. Accumulation fragments...
Autosomal-recessive loss of the NSUN2 gene has been identified as a causative link to intellectual disability disorders in humans. NSun2 is an RNA methyltransferase modifying cytosine-5 transfer RNAs (tRNAs), yet identification cytosine methylation other species hampered by lack sensitive and reliable molecular techniques. Here, we describe miCLIP additional approach for identifying sites transcriptomes. customized version individual-nucleotide-resolution crosslinking immunoprecipitation...
The cohesin protein complex holds sister chromatids in dividing cells together and is essential for chromosome segregation. Recently, has been implicated mediating transcriptional insulation, via its interactions with CTCF. Here, we show different cell types that functionally behaves as a tissue-specific regulator, independent of CTCF binding. By performing matched genome-wide binding assays (ChIP-seq) human breast cancer (MCF-7), discovered thousands genomic sites share estrogen receptor...
Gibbons are small arboreal apes that display an accelerated rate of evolutionary chromosomal rearrangement and occupy a key node in the primate phylogeny between Old World monkeys great apes. Here we present assembly analysis northern white-cheeked gibbon (Nomascus leucogenys) genome. We describe propensity for gibbon-specific retrotransposon (LAVA) to insert into chromosome segregation genes alter transcription by providing premature termination site, suggesting possible molecular mechanism...
Single-cell sequencing of mouse immune cells reveals how aging destabilizes a conserved transcriptional activation program.
A large proportion of functional sequence within mammalian genomes falls outside protein-coding exons and can be transcribed into long RNAs. However, the roles in biology noncoding RNA (lncRNA) are not well understood. Few lncRNAs have experimentally determined roles, with some these being lineage-specific. Determining extent by which transcription lncRNA loci is retained or lost across multiple evolutionary lineages essential if we to understand their contribution lineage-specific traits....
Homologous sets of transcription factors direct conserved tissue-specific gene expression, yet factor-binding events diverge rapidly between closely related species. We used hepatocytes from an aneuploid mouse strain carrying human chromosome 21 to determine, on a chromosomal scale, whether interspecies differences in transcriptional regulation are primarily directed by genetic sequence or nuclear environment. Virtually all locations, landmarks initiation, and the resulting expression...