A5058971107- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Bioinformatics and Genomic Networks
- Fungal and yeast genetics research
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Cancer-related gene regulation
- Animal Genetics and Reproduction
- Cancer Research and Treatments
- Developmental Biology and Gene Regulation
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Chromosomal and Genetic Variations
- Plant and Fungal Interactions Research
- Physical Activity and Health
- Stroke Rehabilitation and Recovery
- Congenital heart defects research
- Hemoglobinopathies and Related Disorders
- Pancreatic function and diabetes
- Biotin and Related Studies
- Biomedical and Chemical Research
- Neurogenesis and neuroplasticity mechanisms
European Molecular Biology Laboratory
2020-2024
European Molecular Biology Laboratory
2020-2024
Max Delbrück Center
2024
Heidelberg University
2014-2017
DKFZ-ZMBH Alliance
2014
Institute of Gene Biology
2013
Moscow State University
2011
Enhancers play a vital role in gene regulation and are critical mediating the impact of noncoding genetic variants associated with complex traits. Enhancer activity is cell-type-specific process regulated by transcription factors (TFs), epigenetic mechanisms variants. Despite strong mechanistic link between TFs enhancers, we currently lack framework for jointly analysing them regulatory networks (GRN). Equally important, an unbiased way assessing biological significance inferred GRNs since...
Abstract The question of how metabolism impacts development is seeing a renaissance [1, 2]. How exerts instructive signaling functions one the central issues that need to be resolved. We tackled this in context mouse embryonic axis segmentation. Previous studies have shown changes carbon impact Wnt [3–6] and period segmentation clock [7], which controls timing Here, we reveal glycolysis tunes an anti-correlated manner: higher glycolytic flux slows down clock, vice versa. Transcriptome gene...
Highlights•The impact of antisense transcription on protein levels is measured for 188 genes•Antisense has mostly weak suppressive effects ∼25% the genes•Regulation by correlates with promoter overlap and H3K4 methylation•Antisense-regulated genes have lower than expected noise levelsSummaryStable unannotated transcripts (SUTs), some which protein-coding in direction, are a class non-coding RNAs. While case studies reported important regulatory roles several such RNAs, their general...
Cellular differentiation requires dramatic changes in chromatin organization, transcriptional regulation, and protein production. To understand the regulatory connections between these processes, we generated proteomic, transcriptomic, accessibility data during of mouse embryonic stem cells (ESCs) into postmitotic neurons found extensive associations different molecular layers within across time points. We observed that SOX2, as a regulator pluripotency neuronal genes, redistributes from...
Here, we report on a novel PCR targeting-based strategy called 'PCR duplication' that enables targeted duplications of genomic regions in the yeast genome using simple PCR-based approach. To demonstrate its application first duplicated promoter FAR1 gene and simultaneously inserted GFP downstream it. This created reporter for activity while leaving fully intact. In another experiment, used duplication to increase dosage discrete manner, from 1× 2x. Using TUB4, encoding γ-tubulin, validated...
Abstract Among the biggest challenges in post-GWAS (genome-wide association studies) era is interpretation of disease-associated genetic variants non-coding genomic regions. Enhancers have emerged as key players mediating effect on complex traits and diseases. Their activity regulated by a combination transcription factors (TFs), epigenetic changes variants. Several approaches exist to link enhancers their target genes, others that infer TF-gene connections. However, we currently lack...
Histone modifications are associated with distinct transcriptional states, but it is unclear whether they instruct gene expression. To investigate this, we mutate histone H3.3 K9 and K27 residues in mouse embryonic stem cells (mESCs). Here, find that H3.3K9 essential for controlling specific distal intergenic regions proper H3K27me3 deposition at promoters. The H3.3K9A mutation resulted decreased H3K9me3 encompassing endogenous retroviruses induced a gain of H3K27ac nascent transcription....
The developmental switch of globin gene expression is a characteristic feature vertebrate organisms. β-globin believed to depend on reconfiguration the active chromatin hub, which contains transcribed genes and regulatory elements. Mechanisms controlling α-globin are less clear. Here, we studied mode packaging chicken domain in red blood cells (RBCs) primitive definite lineages spatial configuration this RBCs lineage. It has been demonstrated that lineage already contain adult-type hub but...
Pervasive transcription of genomes generates multiple classes non-coding RNAs. One these are stable long RNAs which overlap coding genes in antisense direction (asRNAs). The function such asRNAs is not fully understood but several cases antisense-dependent gene expression regulation affecting the overlapping have been demonstrated. Using high-throughput yeast genetics and a limited set four growth conditions we previously reported regulatory for ∼25% asRNAs, most repress sense gene. To...
Abstract Bone marrow mesenchymal stromal cells (BMSCs) can differentiate into adipocytes and osteoblasts, are important regulators of the haematopoietic system. Ageing associates with an increased ratio bone to osteoblasts immune dysregulation. Here, we carried out integrative multiomics analysis ATAC-Seq, RNA-Seq proteomics data from primary human BMSCs in a healthy cohort age between 20 - 60. We identified age-sensitive elements uniquely affecting each molecular level where transcription...
Abstract Lysine-specific demethylase 1 (LSD1/KDM1A) demethylates both histone and non-histone substrates, recruits repressive chromatin complexes, is increased in cancers. De novo LSD1 mutations impairing protein function lead to a rare developmental disorder, but the molecular details of pathology remains unclear. Using patient-derived fibroblasts, reprogrammed pluripotent stem cells, differentiated we found over 4000 differentially expressed genes 68 transcription factors (TFs) whose motif...
Mit einem Festakt und Alumni-Forum begeht das ZMBH am 17. 18. September 2015 sein 30-jahriges Bestehen. An dieser zentralen Forschungseinrichtung der Ruperto Carola widmen sich Wissenschaftler verschiedener Disziplinen Erforschung grundlegender molekular- zellbiologischer Prozesse, die vielfach auch medizinische Aspekte beruhren.
Abstract Histone modifications are associated with distinct transcriptional states, but it is unclear whether they instruct gene expression. To investigate this, we mutated histone H3.3 K9 and K27 residues in mouse embryonic stem cells (mESCs). Here, find that H3.3K9 essential for controlling specific distal intergenic regions proper H3K27me3 deposition at promoters. The H3.3K9A mutation resulted decreased H3K9me3 encompassing endogenous retroviruses induced a gain of H3K27ac nascent...