A5014771943- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- Molecular Biology Techniques and Applications
- 3D Printing in Biomedical Research
- Chromosomal and Genetic Variations
- Animal Genetics and Reproduction
- Advanced biosensing and bioanalysis techniques
- Neuroscience and Neural Engineering
- Microfluidic and Bio-sensing Technologies
- Congenital heart defects research
- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Viral Infectious Diseases and Gene Expression in Insects
- Chromatin Remodeling and Cancer
- DNA and Nucleic Acid Chemistry
- Tissue Engineering and Regenerative Medicine
- Plant Virus Research Studies
- Plant Molecular Biology Research
Stanford University
2020-2025
Bioengineering Center
2021
Abstract Large serine recombinases (LSRs) are DNA integrases that facilitate the site-specific integration of mobile genetic elements into bacterial genomes. Only a few LSRs, such as Bxb1 and PhiC31, have been characterized to date, with limited efficiency tools for in human cells. In this study, we developed computational approach identify thousands LSRs their attachment sites, expanding known LSR diversity by >100-fold enabling prediction insertion site specificities. We tested...
Short tandem repeats (STRs) are enriched in eukaryotic cis-regulatory elements and alter gene expression, yet how they regulate transcription remains unknown. We found that STRs modulate factor (TF)-DNA affinities apparent on-rates by about 70-fold directly binding TF DNA-binding domains, with energetic impacts exceeding many consensus motif mutations. maximize the number of weakly preferred microstates near target sites, thereby increasing density, well predicted statistical mechanics....
The binding of multiple transcription factors (TFs) to genomic enhancers activates gene expression in mammalian cells. However, the molecular details that link enhancer sequence TF binding, promoter state, and levels remain opaque. We applied single-molecule footprinting (SMF) measure simultaneous occupancy TFs, nucleosomes, components machinery on engineered enhancer/promoter constructs with variable numbers sites for both a synthetic an endogenous TF. find activation domains enhance TF's...
The molecular details governing transcription factor (TF) binding and the formation of accessible chromatin are not yet quantitatively understood - including how sequence context modulates affinity, TFs search DNA, kinetics TF occupancy, motif grammars coordinate binding. To resolve these questions for a human TF, erythroid Kruppel-like (eKLF/KLF1), we compare, in high throughput, vitro rates affinities with vivo single molecule nucleosome occupancies across engineered DNA sequences. We find...
Abstract Short tandem repeats (STRs) are enriched in eukaryotic cis -regulatory elements and their polymorphisms alter gene expression, yet how they regulate transcription remains unknown. We find that STRs can modulate factor (TF)-DNA affinities on rates by up to 70-fold directly binding TF DNA-binding domains, with energetic impacts approaching or exceeding mutations consensus sites. maximize the number of weakly preferred microstates near target sites, thereby increasing density motifs...
SUMMARY Recent microbial genome sequencing efforts have revealed a vast reservoir of mobile genetic elements containing integrases that could be useful engineering tools. Large serine recombinases (LSRs), such as Bxb1 and PhiC31, are bacteriophage-encoded can facilitate the insertion phage DNA into bacterial genomes. However, only few LSRs been previously characterized they limited efficiency in human cells. Here, we developed systematic computational discovery workflow identifies thousands...
Summary Organoids are powerful experimental models for studying the ontogeny and progression of diseases including cancer. conventionally cultured in bulk using an extracellular matrix mimic. However, organoids culture physically overlap, making it impossible to track growth individual over time high throughput. Moreover, local spatial variations properties make difficult assess whether observed phenotypic heterogeneity between results from intrinsic cell differences or microenvironment...