A5003254774- RNA Research and Splicing
- Fungal and yeast genetics research
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
- Gene Regulatory Network Analysis
- HVDC Systems and Fault Protection
- Bioinformatics and Genomic Networks
- DNA Repair Mechanisms
- Cancer-related molecular mechanisms research
- CRISPR and Genetic Engineering
- Plant Reproductive Biology
- Gene expression and cancer classification
- Plant Molecular Biology Research
- Epigenetics and DNA Methylation
- Yeasts and Rust Fungi Studies
- Horticultural and Viticultural Research
- Plant and Fungal Interactions Research
- Genomics and Phylogenetic Studies
- Biotin and Related Studies
- Photosynthetic Processes and Mechanisms
- Genetics and Neurodevelopmental Disorders
- Folate and B Vitamins Research
- Peptidase Inhibition and Analysis
The Francis Crick Institute
2016-2024
Weizmann Institute of Science
2023
Human Technopole
2023
Whitehead Institute for Biomedical Research
2023
Charité - Universitätsmedizin Berlin
2023
The Honourable Society of Lincoln's Inn
2016
Howard Hughes Medical Institute
2011-2013
Massachusetts Institute of Technology
2011-2013
Google (United States)
2011
University Medical Center Utrecht
2006-2009
Cell size varies greatly between cell types, yet within a specific type and growth condition, is narrowly distributed. Why maintenance of cell-type important remains poorly understood. Here we show that growing budding yeast primary mammalian cells beyond certain impairs gene induction, cell-cycle progression, signaling. These defects are due to the inability large scale nucleic acid protein biosynthesis in accordance with volume increase, which effectively leads cytoplasm dilution. We...
Abstract RNA molecules undergo a vast array of chemical post-transcriptional modifications (PTMs) that can affect their structure and interaction properties. In recent years, growing number PTMs have been successfully mapped to the transcriptome using experimental approaches relying on high-throughput sequencing. Oxford Nanopore direct-RNA sequencing has shown be sensitive modifications. We developed validated Nanocompore, robust analytical framework identifies from these data. Our strategy...
Differentiation programs such as meiosis depend on extensive gene regulation to mediate cellular morphogenesis. Meiosis requires transient removal of the outer kinetochore, complex that connects microtubules chromosomes. How meiotic expression program temporally restricts kinetochore function is unknown. We discovered in budding yeast, inactivation occurs by reducing abundance a limiting subunit, Ndc80. Furthermore, we uncovered an integrated mechanism acts at transcriptional and...
Production of haploid gametes from diploid progenitor cells is mediated by a specialized cell division, meiosis, where two divisions, meiosis I and II, follow single S phase. Errors in progression to II lead aneuploid polyploid gametes, but the regulatory mechanisms controlling this transition are poorly understood. Here, we demonstrate that conserved kinase Ime2 regulates timing order meiotic divisions translation. coordinates translational activation cluster genes at I–meiosis transition,...
Cell differentiation programs require dynamic regulation of gene expression. During meiotic prophase in Saccharomyces cerevisiae, expression the kinetochore complex subunit Ndc80 is downregulated by a 5’ extended long undecoded NDC80 transcript isoform. Here we demonstrate transcriptional interference mechanism that responsible for inhibiting coding mRNA Transcription from distal promoter directs Set1-dependent histone H3K4 dimethylation and Set2-dependent H3K36 trimethylation to establish...
Abstract Background The start and end sites of messenger RNAs (TSSs TESs) are highly regulated, often in a cell-type-specific manner. Yet the contribution transcript diversity regulating gene expression remains largely elusive. We perform an integrative analysis multiple synchronized cell-fate transitions quantitative genomic techniques Saccharomyces cerevisiae to identify regulatory functions associated with transcribing alternative isoforms. Results Cell-fate feature widespread elevated...
N6-methyladenosine (m6A) is a widely studied and abundant RNA modification. The m6A mark regulates the fate of RNAs in various ways, which turn drives changes cell physiology, development, disease pathology. Over last decade, numerous methods have been developed to map quantify sites genome-wide through deep sequencing. Alternatively, levels can be quantified from population using techniques such as liquid chromatography-mass spectrometry or thin layer chromatography. However, many for...
Transcription of long noncoding RNAs (lncRNAs) regulates local gene expression in eukaryotes. Many examples how a single lncRNA controls the an adjacent or nearby protein-coding have been described. Here we examine regulation locus consisting two contiguous lncRNAs and master regulator for entry into yeast meiosis, IME1. We find that cluster together with several transcription factors form regulatory circuit by which IME1 its own promoter thereby promotes expression. Inhibition stimulation...
methyladenosine (m6A) RNA modification impacts mRNA fate primarily via reader proteins, which dictate processes in development, stress, and disease. Yet little is known about m6A function
Most genes are transcribed from multiple transcription start sites (TSSs), defined as alternative TSSs, which highly regulated and can lead to various gene regulatory outcomes including changes in translation efficiency protein isoform expression. Transcription factors chromatin regulators control TSS selection. DNA supercoiling affects aspects of initiation; however, its effect on with TSSs is not known. Here, we investigated how impacts usage Saccharomyces cerevisiae. We depleted...
Transcription initiation is a highly dynamic and tightly regulated process involving the coordinated action of transcription factors, chromatin remodelers, RNA polymerase which determine where when begins. Accurately mapping quantifying start sites (TSSs) from nascently transcribed RNAs remains key area interest, as it provides critical insights into dynamics. Here, we combined transient transcriptome sequencing with site (TT-TSS-seq) to accurately map quantify nascent transcripts. Since...
Promoter recognition by TATA-binding protein (TBP) is an essential step in the initiation of RNA polymerase II (pol II) mediated transcription. Genetic and biochemical studies yeast have shown that Mot1p NC2 play important roles inhibiting TBP activity. To understand how activity regulated a genome-wide manner, we profiled binding TBP, NC2, Mot1p, TFIID, SAGA, pol across genome using chromatin immunoprecipitation (ChIP)–chip for cells exponential growth during reprogramming We find...
Highlights•Expression of divergent noncoding RNAs is repressed by Rap1•Rap1 prevents initiation transcription near its binding sites•Rap1 provides directionality toward productive transcriptionSummaryMany active eukaryotic gene promoters exhibit transcription, but the mechanisms restricting expression these transcripts are not well understood. Here, we demonstrate how a sequence-specific factor represses at highly expressed genes in yeast. We find that depletion Rap1 induces large fraction...
Cell fate choices are tightly controlled by the interplay between intrinsic and extrinsic signals, gene regulatory networks. In Saccharomyces cerevisiae, decision to enter into gametogenesis or sporulation is dictated mating type nutrient availability. These signals regulate expression of master regulator gametogenesis, IME1. Here we describe how nutrients control IME1 expression. We find that protein kinase A (PKA) target rapamycin complex I (TORC1) signalling mediate regulation Inhibiting...
Abstract Yeast cells enter and undergo gametogenesis relatively asynchronously, making it technically challenging to perform stage-specific genomic biochemical analyses. Cell-to-cell variation in the expression of master regulator entry into sporulation, IME1, has been implicated be underlying cause asynchronous sporulation. Here, we find that timing IME1 is critical importance for inducing sporulation synchronously. When force from an inducible promoter incubated medium 2 hr, vast majority...
Long undecoded transcript isoforms (LUTIs) represent a class of non-canonical mRNAs that downregulate gene expression through the combined act transcriptional and translational repression. While single studies revealed important aspects LUTI-based repression, how these features affect regulation on global scale is unknown. Using leader direct RNA sequencing, here, we identify 74 LUTI candidates are specifically induced in meiotic prophase. Translational repression appears to be ubiquitous...
N6 -methyladenosine (m6A), the most abundant mRNA modification, is deposited in mammals/insects/plants by m6A methyltransferase complexes (MTC) comprising a catalytic subunit and at least five additional proteins. The yeast MTC critical for meiosis was known to comprise three proteins, of which two were conserved. We uncover novel components (Kar4/Ygl036w-Vir1/Dyn2). All subunits, except Dyn2, are essential deposition have corresponding mammalian orthologues. Unlike bipartite MTC,...
Affinity tagging has been used in many global studies towards protein function. We describe a highly efficient system for vivo biotinylation of transcription factors the yeast Saccharomyces cerevisiae, which is based on bacterial BirA biotin ligase. The strength biotin–streptavidin interaction was exploited to improve detection protein–DNA complexes chromatin immunoprecipitation (ChIP) experiments. In test using biotin-tagged LexA DNA-binding protein, we found that stringent washing...
Abstract Intrinsic signals and external cues from the environment drive cell fate decisions. In budding yeast, decision to enter meiosis is controlled by nutrient mating-type that regulate expression of master transcription factor for meiotic entry, IME1 . How control remains poorly understood. Here, we show regulated multiple sequence-specific factors (TFs) mediate association Tup1-Cyc8 co-repressor its promoter. We find at least eight TFs bind promoter when nutrients are ample. Remarkably,...
Chromatin immunoprecipitation combined with DNA microarrays (ChIP-chip) is a powerful technique to detect in vivo protein-DNA interactions. Due low yields, ChIP assays of transcription factors generally require amplification immunoprecipitated genomic DNA. Here, we present an adapted linear method that involves two rounds T7 RNA polymerase (double-T7). Using this could successfully amplify as little 0.4 ng sufficient amounts for microarray analysis. In addition, compared the double-T7...
Met-overaccumulating mutants provide a powerful genetic tool for examining both the regulation of Met biosynthetic pathway and in vivo developmental responses gene expression to altered levels. We have previously reported identification two Arabidopsis thaliana over-accumulation (mto) mutants, mto1-1 mto2-1, that carry mutations genes encoding cystathionine γ-synthase (CGS) threonine synthase (TS), respectively. A third mutant, mto3-1, has recently been mutation S-adenosylmethionine...