A5071071269- Circadian rhythm and melatonin
- Light effects on plants
- Genomics and Chromatin Dynamics
- Chemical Synthesis and Analysis
- Organoboron and organosilicon chemistry
- Epigenetics and DNA Methylation
- Photosynthetic Processes and Mechanisms
- Bacterial biofilms and quorum sensing
- Cancer-related gene regulation
- Vibrio bacteria research studies
- Advanced Electron Microscopy Techniques and Applications
- Genetics, Aging, and Longevity in Model Organisms
- Plant Molecular Biology Research
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Spaceflight effects on biology
- Photoreceptor and optogenetics research
- CRISPR and Genetic Engineering
- DNA and Nucleic Acid Chemistry
- Signaling Pathways in Disease
- Neurobiology and Insect Physiology Research
- Boron Compounds in Chemistry
- Lipid Membrane Structure and Behavior
- Electrohydrodynamics and Fluid Dynamics
- Pluripotent Stem Cells Research
University of Basel
2024
Institute of Science and Technology Austria
2024
Friedrich Miescher Institute
2018-2023
University of California, Santa Cruz
2013-2020
University of San Diego
2014-2015
Western Washington University
2014
Transcription factors (TFs) regulate gene expression through chromatin where nucleosomes restrict DNA access. To study how TFs bind nucleosome-occupied motifs, we focused on the reprogramming OCT4 and SOX2 in mouse embryonic stem cells. We determined TF engagement throughout a nucleosome at base-pair resolution vitro, enabling structure determination by cryo-electron microscopy two preferred positions. Depending motif location, differentially distort nucleosomal DNA. At one position,...
Abstract The basic helix–loop–helix (bHLH) family of transcription factors recognizes DNA motifs known as E-boxes (CANNTG) and includes 108 members 1 . Here we investigate how chromatinized are engaged by two structurally diverse bHLH proteins: the proto-oncogene MYC-MAX circadian factor CLOCK-BMAL1 (refs. 2,3 ). Both bind to preferentially near nucleosomal entry–exit sites. Structural studies with engineered or native nucleosome sequences show that triggers release from histones gain...
Molecular clockwork from cyanobacteria The cyanobacterial circadian clock oscillator can be reconstituted in a test tube just three proteins—KaiA, KaiB, and KaiC—and adenosine triphosphate (ATP). Tseng et al. studied crystal nuclear magnetic resonance structures of complexes the proteins their signaling output tested vivo effects structure-based mutants. Large conformational changes KaiB ATP hydrolysis by KaiC are coordinated with binding to protein, which couples day-night transitions...
Significance Circadian rhythms depend upon the precise coordination of protein interactions within transcription–translation feedback loop molecular clock. Period (PER) and cryptochrome (CRY) rhythmically repress activity circadian transcription factor, CLOCK:BMAL1 (brain muscle Arnt-like 1), to establish daily patterns gene expression. CRY1 binds with without PER inhibit activity. Here we show that interacts CLOCK PAS-B domain dock factor into secondary pocket CRY1. Studies a...
Mammalian circadian rhythms are generated by a transcription-based feedback loop in which CLOCK:BMAL1 drives transcription of its repressors (PER1/2, CRY1/2), ultimately interact with to close the ~24 hr periodicity. Here we pinpoint key difference between CRY1 and CRY2 that underlies their differential strengths as transcriptional repressors. Both cryptochromes bind BMAL1 transactivation domain similarly sequester it from coactivators repress activity. However, find is recruited much higher...
Biofilm formation is critical for the infection cycle of Vibrio cholerae. exopolysaccharides (VPS) and matrix proteins RbmA, Bap1 RbmC are required development biofilm architecture. We demonstrate that RbmA binds VPS directly uses a binary structural switch within its first fibronectin type III (FnIII-1) domain to control dynamics VPS-dependent higher-order structures. The in FnIII-1 regulates interactions trans with FnIII-2 domain, leading open (monomeric) or closed (dimeric) interfaces....
The genomic binding sites of the transcription factor (TF) and tumor suppressor p53 are unusually diverse with regard to their chromatin features, including histone modifications, raising possibility that local environment can contextualize regulation. Here, we show epigenetic characteristics closed chromatin, such as DNA methylation, do not influence across genome. Instead, ability open activate its target genes is locally restricted by cofactor Trim24. Trim24 binds both unmethylated 3...
Cytological profiling (CP) is an unbiased image-based screening technique that uses automated microscopy and image analysis to profile compounds based on numerous quantifiable phenotypic features. We used CP evaluate a library of nearly 500 with documented mechanisms action (MOAs) spanning wide range biological pathways. developed informatics techniques for generating dosage-independent "fingerprints" each compound, quantifying the likelihood compound's fingerprint corresponds its annotated...
The copper-catalyzed diboration of ketones followed by an acid-catalyzed elimination leads to the formation 1,1-disubstituted and trisubstituted vinyl boronate esters with moderate good yields selectivity. Addition tosic acid crude products provides corresponding upon elimination. are formed as (Z)-olefin isomer, which was established subjecting a Suzuki-Miyaura coupling reaction obtain alkenes known geometry.
Abstract In situ cryo-electron tomography (cryo-ET) has emerged as the method of choice to investigate structures biomolecules in their native context. However, challenges remain efficient production large-scale cryo-ET datasets, well community sharing this information-rich data. Here, we applied a cryogenic plasma-based focused ion beam (cryo-PFIB) instrument for high-throughput milling green alga Chlamydomonas reinhardtii , useful model organism visualization numerous fundamental cellular...
Summary Circadian rhythms are generated by a transcription-based feedback loop where CLOCK:BMAL1 drive transcription of their repressors (PER1/2, CRY1/2), which bind to close the with ~24-hour periodicity. Here we identify key biochemical and structural difference between CRY1 CRY2 that underlies differential strengths as transcriptional repressors. While both cryptochromes BMAL1 transactivation domain similar affinity sequester it from coactivators, is recruited much higher PAS core...
Abstract The genomic binding sites of the transcription factor (TF) and tumour suppressor p53 are unusually diverse in regards to their chromatin features, including histone modifications, opening possibility that provides context-dependence for regulation. Here, we show ability open activate its target genes is indeed locally restricted by cofactor Trim24. Trim24 binds both unmethylated lysine 4 H3, thereby preferentially locating those reside closed chromatin, while it deterred from...