- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- Plant Molecular Biology Research
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
Stanford University
2024-2025
University of Pennsylvania
2019-2022
Children's Hospital of Philadelphia
2022
Although critical for tuning the timing and level of transcription, enhancer communication with distal promoters is not well understood. Here, we bypass need sequence-specific transcription factors (TFs) recruit activators directly using a chimeric array gRNA oligos to target dCas9 fused activator VP64-p65-Rta (CARGO-VPR). We show that this approach achieves effective recruitment arbitrary genomic sites, even those inaccessible when targeted single guide. utilize CARGO-VPR across Prdm8-Fgf5...
The formation and spatial arrangement of chromosome territories (CTs) in interphase has been posited to influence the outcome frequency genomic translocations. This is supported by correlations between inter-chromosomal contacts translocation events myriad systems. However, it remains unclear if CT itself influences potential cells. We address this question Drosophila cells modulating level Condensin II, which regulates organization. Using whole-chromosome Oligopaints identify...
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 The environment encountered by an organism can modulate epigenetic information in gametes to transmit non-genetically inherited phenotypes offspring. In mouse models, the diet of males regulates specific tRNA-derived RNAs (tDRs) sperm. After fertilization, tDRs regulate embryonic gene expression and generate metabolic adult offspring through uncharacterized changes during development. Here we demonstrate that C. elegans, also accumulate sperm similarly epigenetically We identify...
While critical for tuning the timing and level of transcription, enhancer communication with distal promoters is not well understood. Here we bypass need sequence-specific transcription factors recruit activators directly using CARGO-VPR, an approach targeting dCas9-VPR a multiplexed array RNA guides. We show that this achieves effective activator recruitment to arbitrary genomic sites, even those inaccessible by single dCas9. utilize CARGO-VPR across