A5037119286- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- RNA modifications and cancer
- Histone Deacetylase Inhibitors Research
- Nuclear Structure and Function
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Acute Myeloid Leukemia Research
- Genetics and Neurodevelopmental Disorders
- DNA Repair Mechanisms
- Oxidative Organic Chemistry Reactions
- Genetic Syndromes and Imprinting
- Catalytic C–H Functionalization Methods
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Radical Photochemical Reactions
Broad Institute
2022-2025
Harvard University
2019-2025
Harvard University Press
2024
University of Pennsylvania
2017
An operationally simple, mild, redox-neutral method for the photoredox alkylation of imines is reported. Utilizing an inexpensive organic catalyst, alkyl radicals are readily generated from single-electron oxidation ammonium bis(catecholato)silicates and subsequently engaged in a C-C bond-forming reaction with imines. The process highly selective, metal-free, does not require large excess alkylating reagent or use acidic additives.
Abstract The genome can be divided into two spatially segregated compartments, A and B, which partition active inactive chromatin states. While constitutive heterochromatin is predominantly located within the B compartment near nuclear lamina, facultative marked by H3K27me3 spans both compartments. How epigenetic modifications, compartmentalization, lamina association collectively maintain architecture remains unclear. Here we develop Lamina-Inducible Methylation Hi-C (LIMe-Hi-C) to jointly...
Abstract The interchromatin space in the cell nucleus contains various membrane-less nuclear bodies. Recent findings indicate that speckles, comprising a distinct body, exhibit interactions with certain chromatin regions ground state. Key questions are how this state of chromatin-nuclear speckle association is established and what gene regulatory roles layer organization. We report here structural factors CTCF cohesin required for full between DNA speckles. Disruption DNA-speckle contacts...
Abstract The insulator protein CTCF is essential for mediating chromatin loops and regulating gene expression. While it established that DNA methylation hinders binding, the impacts of this methylation-sensitive binding on architecture transcription are poorly defined. Here, we used a selective DNMT1 inhibitor to investigate characteristics functions ‘reactivated’ peaks resulting from global demethylation. We found reactivated preferentially form bodies interact with highly-looping partner...
The insulator protein CTCF is essential for mediating chromatin loops and regulating gene expression. While it established that DNA methylation hinders binding, the impacts of this methylation-sensitive binding on architecture transcription are poorly defined. Here, we used a selective DNMT1 inhibitor to investigate characteristics functions ‘reactivated’ peaks resulting from global demethylation. We found reactivated preferentially form bodies interact with highly-looping partner located in...
The insulator protein CTCF is essential for mediating chromatin loops and regulating gene expression. While it established that DNA methylation hinders binding, the impacts of this methylation-sensitive binding on architecture transcription are poorly defined. Here, we used a selective DNMT1 inhibitor to investigate characteristics functions ‘reactivated’ peaks resulting from global demethylation. We found reactivated preferentially form bodies interact with highly-looping partner located in...
Genome editing enables sequence-function profiling of endogenous cis-regulatory elements, driving understanding their mechanisms and the development gene therapies. However, these approaches cannot be combined with direct scalable readouts chromatin structure accessibility across long single-molecule fibers. Here we leverage a double-stranded DNA cytosine deaminase to profile at high depth resolution loci interest through targeted PCR long-read sequencing, method term deaminase-accessible...
Abstract Cancer mutations in Polycomb Repressive Complex 2 (PRC2) drive aberrant epigenetic states. Although therapies inhibiting the PRC2 enzymatic component EZH2 are FDA-approved, oncogene-specific dependencies remain to be discovered. Here, we identify that confer both resistance and drug addiction inhibitors EZH2-mutant lymphoma, resulting cancer cells paradoxically depend on for survival. Drug is mediated by hypermorphic CXC domain of EZH2, which maintain H3K27me3 levels even presence...
Abstract Drug addiction, a phenomenon where cancer cells paradoxically depend on continuous drug treatment for survival, has uncovered cell signaling mechanisms and co-dependencies. Here, we discover mutations that confer addiction to inhibitors of the transcriptional repressor Polycomb Repressive Complex 2 (PRC2) in diffuse large B-cell lymphoma (DLBCL). is mediated by hypermorphic CXC domain catalytic subunit EZH2, which maintain H3K27me3 levels even presence PRC2 inhibitors....
Abstract The genome can be divided into two spatially segregated compartments, A and B, 1,2 which broadly partition active inactive chromatin states, respectively. Constitutive heterochromatin is predominantly located within the B compartment comprises that in close contact with nuclear lamina. 3–5 By contrast, facultative marked by H3K27me3 span both compartments. 2–5 How epigenetic modifications, A/B compartmentalization, lamina association collectively maintain architecture function...