A5044791324- Genetics, Aging, and Longevity in Model Organisms
- Pluripotent Stem Cells Research
- Cell Adhesion Molecules Research
- Glycosylation and Glycoproteins Research
- CRISPR and Genetic Engineering
- Galectins and Cancer Biology
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Reproductive Biology and Fertility
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Circadian rhythm and melatonin
- Tissue Engineering and Regenerative Medicine
- Cardiomyopathy and Myosin Studies
- Cancer-related gene regulation
- Enzyme Structure and Function
- Autophagy in Disease and Therapy
- Photosynthetic Processes and Mechanisms
- Congenital heart defects research
- Axon Guidance and Neuronal Signaling
- Animal Genetics and Reproduction
- Plant Molecular Biology Research
- FOXO transcription factor regulation
- Adipose Tissue and Metabolism
Universität Hamburg
2002-2024
Max Delbrück Center
2012-2023
MSB Medical School Berlin
2018-2022
InSysBio (Russia)
2020
Howard Hughes Medical Institute
2009-2013
Columbia University Irving Medical Center
2009-2013
Columbia University
2007
University of Massachusetts Chan Medical School
2006-2007
Removal of a chromatin factor allows transcription factors to reprogram germ cells into neurons.
Engineering fluorescent proteins into large genomic clones, contained within BACs or fosmid vectors, is a tool to visualize and study spatiotemporal gene expression patterns in transgenic animals. Because these reporters cover regions, they most likely capture all cis-regulatory information can therefore be expected recapitulate aspects of endogenous expression. Inserting tags at the target locus clones by homologous recombination ("recombineering") represents straightforward method generate...
How specific cell types can be directly converted into other distinct is a matter of intense investigation with wide-ranging basic and biomedical implications. Here, we show that removal the histone 3 lysine 27 (H3K27) methyltransferase Polycomb repressor complex 2 (PRC2) permits ectopically expressed, neuron-type-specific transcription factors ("terminal selectors") to convert Caenorhabditis elegans germ cells neuron types. Terminal-selector-induced germ-cell-to-neuron conversion observed...
Highlights•Chromatin regulator FACT blocks cellular reprogramming in C. elegans and humans•FACT maintains cell fates antagonizes induction of ectopic elegans•FACT depletion human cells primes the transcriptome for reprogrammingSummaryThe chromatin (facilitates transcription) is essential ensuring stable gene expression by promoting transcription. In a genetic screen using Caenorhabditis elegans, we identified that identities acts as barrier transcription factor-mediated fate reprogramming....
Autophagy is a ubiquitous catabolic process that causes cellular bulk degradation of cytoplasmic components and generally associated with positive effects on health longevity. Inactivation autophagy has been linked detrimental cells organisms. The antagonistic pleiotropy theory postulates some fitness-promoting genes during youth are harmful aging. On this basis, we examined mediating post-reproductive longevity using an RNAi screen. From screen, identified 30 novel regulators longevity,...
High-occupancy target (HOT) regions are segments of the genome with unusually high number transcription factor binding sites. These observed in multiple species and thought to have biological importance due occupancy. Furthermore, they coincide house-keeping gene promoters consequently associated genes stably expressed across cell types. Despite these features, HOT solely defined using ChIP-seq experiments shown lack canonical motifs for factors that be bound there. Although, golden standard...
LIM kinase 1 (LIMK1) controls important cellular functions such as morphogenesis, cell motility, tumor metastasis, development of neuronal projections, and growth cone actin dynamics. We have investigated the role RING finger protein Rnf6 during detected high levels in developing axonal projections motor DRG neurons mouse embryogenesis well cultured hippocampal neurons. RNAi-mediated knock-down experiments primary identified a regulator axon outgrowth. Consistent with growth, we found that...
Abstract Mammary oncogenesis is profoundly influenced by signaling pathways controlled estrogen receptor α (ERα). Although it known that ERα exerts its oncogenic effect stimulating the proliferation of many human breast cancers through activation target genes, our knowledge underlying transcriptional mechanisms remains limited. Our published work has shown in vivo activity LIM homeodomain transcription factors (LIM-HD) critically regulated cofactors LIM-HD proteins (CLIM) and ubiquitin...
Affinity purification followed by mass spectrometry (AP/MS) is a widely used approach to identify protein interactions and complexes. In multicellular organisms, the accurate identification of complexes AP/MS complicated potential heterogeneity in different tissues. Here, we present an vivo biotinylation-based for tissue-specific from Caenorhabditis elegans. Tissue-specific biotinylation achieved expression select tissues bacterial biotin ligase BirA, which biotinylates proteins tagged with...
Abstract Chromatin regulators play important roles in the safeguarding of cell identities by opposing induction ectopic fates and, thereby, preventing forced conversion reprogramming approaches. Our knowledge chromatin acting as barriers living organisms needs improvement most studies use tissue culture. We used Caenorhabditis elegans an vivo gene discovery model and automated solid-phase RNA interference screening, which we identified 10 chromatin-regulating factors that protect cells...
Cell-fate reprograming is at the heart of development, yet very little known about molecular mechanisms promoting or inhibiting in intact organisms. In C. elegans germline, germ cells into somatic requires chromatin perturbation. Here, we describe that such facilitated by GLP-1/Notch signaling pathway. This surprising, since this pathway best for maintaining undifferentiated germline stem cells/progenitors. Through a combination genetics, tissue-specific transcriptome analysis, and...
An understanding of the molecular mechanisms cell fate determination in nervous system requires elucidation transcriptional regulatory programs that ultimately control neuron-type-specific gene expression profiles. We show here C. elegans Tailless/TLX-type, orphan nuclear receptor NHR-67 acts at several distinct steps to determine identity and subsequent left/right (L/R) asymmetric subtype diversification a class gustatory neurons, ASE neurons. nhr-67 controls broad aspects sensory neuron...
Abstract Muscle atrophy is a physiological response to disuse and malnutrition, but hibernating bears are largely resistant this phenomenon. Unlike other mammals, they efficiently reabsorb amino acids from urine, periodically activate muscle contraction, their adipocytes differentially responds insulin. The contribution of myocytes the reduced remains unknown. Here we show how metabolism signaling regulated in skeletal grizzly bear. Metabolic modeling proteomic changes suggests an autonomous...
Complexes composed of multiple proteins regulate most cellular functions. However, our knowledge about the molecular mechanisms governing assembly and dynamics these complexes in cells remains limited. The vivo activity LIM homeodomain (LIM-HD) proteins, a class transcription factors that regulates neuronal development, depends on high-affinity association their domains with cofactor (LIM-HDs) (CLIM, also known as Ldb or NLI). CLIM cofactors recruit single-stranded DNA-binding protein 1...
Transcriptional co-repressors of the Groucho/TLE family are important regulators development in many species. A subset members that lack C-terminal WD40 domains have been proposed to act as dominant-negative proteins, yet such a role has not conclusively proven. Through mutant screen for genes controlling left/right asymmetric cell fate decision nervous system nematode C. elegans, we retrieved loss-of-function alleles two distinct loci display identical phenotypes neuronal specification and...
Left/right asymmetric features of animals are either randomly distributed on the left or right side within a population (“antisymmetries”) found stereotypically one particular an animal (“directional asymmetries”). Both types asymmetries can be in nervous systems, but whether regulatory programs that establish these share any mechanistic is not known. We describe here unprecedented molecular link between two Caenorhabditis elegans . The zinc finger transcription factor die-1 expressed...
Abstract Divergent transcription from promoters and enhancers is pervasive in many species, but it remains unclear if a general feature of all eukaryotic cis regulatory elements. To address this, here we define elements C. elegans , D. melanogaster H. sapiens investigate the determinants their directionality. In three find that divergent initiated two separate core promoter sequences regions display competition between histone modifications on + 1 −1 nucleosomes. contrast, directionality,...
Whether extension of lifespan provides an extended time without health deteriorations is important issue for human aging. However, to which degree and aspects healthspan regulation might be linked not well understood. Chromatin factors could involved in linking both aging aspects, as epigenetic mechanisms bridge different biological processes. The factor LIN-53 (RBBP4/7) associates with chromatin-regulating complexes safeguard cell identities Caenorhabditis elegans mammals, has a role...
Abstract The developmental regulation of LIM homeodomain transcription factors (LIM‐HD) by the domain‐binding cofactors CLIM/Ldb/NLI and RLIM has been demonstrated. Whereas CLIM are thought to be required for at least some in vivo functions LIM‐HD proteins, ubiquitin ligase as a negative regulator its ability target proteasomal degradation. In this report, we have investigated compared protein expression both developing mouse neural tube. We co‐localize proteins many tissues and, although...
Epigenetic mechanisms control chromatin accessibility and gene expression to ensure proper cell fate specification. Histone proteins are integral components, their modification promotes regulation. Specific recognize modified histones such as the chromodomain protein MRG-1. MRG-1 is Caenorhabditis elegans ortholog of mammalian MRG15, which involved in DNA repair. binds methylated histone H3 important for germline maturation safeguarding. To elucidate interacting that modulate activity, we...
3′ Untranslated region (UTR)-dependent post-transcriptional regulation has emerged as a critical mechanism of controlling gene expression in various physiological contexts, including cellular differentiation events. Here, we examine the 3′UTR die-1 transcription factor single neuron nematode C. elegans . This shows intriguing feature being differentially regulated across animal's left/right axis. In left gustatory neuron, ASEL, which DIE-1 protein is normally expressed adult animals, confers...