A5015797783- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- Erythrocyte Function and Pathophysiology
- DNA and Nucleic Acid Chemistry
- Nuclear Structure and Function
- Amyotrophic Lateral Sclerosis Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Biochemical and Molecular Research
- Enzyme Structure and Function
- Nanoparticles: synthesis and applications
- Legionella and Acanthamoeba research
- TGF-β signaling in diseases
- Genetics, Aging, and Longevity in Model Organisms
- Neurogenetic and Muscular Disorders Research
- Bacteriophages and microbial interactions
- Cancer-related gene regulation
- American Literature and Culture
- Neuroscience and Neural Engineering
- Autophagy in Disease and Therapy
- Genetics and Neurodevelopmental Disorders
University of California, Berkeley
2022-2024
University of California, San Francisco
2020-2021
Cornell University
2012-2017
Oregon State University
2011
In mammals, HP1-mediated heterochromatin forms positionally and mechanically stable genomic domains even though the component HP1 paralogs, HP1α, HP1β, HP1γ, display rapid on-off dynamics. Here, we investigate whether phase-separation by proteins can explain these biological observations. Using bulk single-molecule methods, show that, within phase-separated HP1α-DNA condensates, HP1α acts as a dynamic liquid, while compacted DNA molecules are constrained in local territories. These...
Legionella pneumophila is an opportunistic intracellular pathogen that causes sporadic and epidemic cases of Legionnaires’ disease. Emerging data suggest infection involves the subversion host phosphoinositide (PI) metabolism. However, how this bacterium actively manipulates PI lipids to benefit its still enigma. Here, we report L. virulence factor SidF a phosphatidylinositol polyphosphate 3-phosphatase specifically hydrolyzes D3 phosphate PI(3,4)P 2 PI(3,4,5)P 3 . This activity necessary...
The spatial segregation of pericentromeric heterochromatin (PCH) into distinct, membrane-less nuclear compartments involves the binding Heterochromatin Protein 1 (HP1) to H3K9me2/3-rich genomic regions. While HP1 exhibits liquid–liquid phase separation properties in vitro, its mechanistic impact on structure and dynamics PCH condensate formation vivo remains largely unresolved. Here, using a minimal theoretical framework, we systematically investigate mutual coupling between self-interacting...
Proper cell function requires preservation of the spatial organization chromatin modifications. Maintenance this epigenetic landscape necessitates transfer parental nucleosomes to newly replicated DNA, a process that is stringently regulated and intrinsically linked replication fork dynamics. This creates formidable setting from which isolate central mechanism transfer. Here we utilized minimal experimental system track fate single nucleosome following its displacement, examined whether DNA...
In mammals HP1-mediated heterochromatin forms positionally and mechanically stable genomic domains even though the component HP1 paralogs, α , β γ display rapid on-off dynamics. Here we investigate whether phase-separation by proteins can explain these biological observations. Using bulk single-molecule methods, show that, within phase-separated -DNA condensates, acts as a dynamic liquid, while compacted DNA molecules are constrained in local territories. These condensates resistant to large...
The introduction of chemical inhibitors into living cells at specific times in development is a useful method for investigating the roles proteins or cytoskeletal components developmental processes. Some embryos, such as those Caenorhabditis elegans, however, possess tough eggshell that makes introducing drugs and other molecules embryonic challenging. We have developed procedure using carbon-reinforced nanopipettes (CRNPs) to deliver C. elegans embryos with high temporal control. use CRNPs...
ABSTRACT The spatial segregation of pericentromeric heterochromatin (PCH) into distinct, membrane-less nuclear compartments involves the binding Heterochromatin Protein 1 (HP1) to H3K9me2/3-rich genomic regions. While HP1 exhibits liquid-liquid phase separation properties in vitro , its mechanistic impact on structure and dynamics PCH condensate formation vivo remains largely unresolved. Here, using biophysical modeling, we systematically investigate mutual coupling between self-interacting...
Abstract Compartmentalization of the nucleus into heterochromatin and euchromatin is highly conserved across eukaryotes. Constitutive (C-Het) constitutes a liquid-like condensate that packages repetitive regions genome through enrichment histone modification H3K9me3 recruitment its cognate reader protein Heterochromatin Protein-1 (HP1a). The ability for well-ordered nucleosome arrays HP1a to independently form biomolecular condensates suggests emergent material properties C-Het compartments...
Formation of the heterochromatin nuclear compartment is initiated by methylation histone H3 K9 and its subsequent binding Heterochromatin Protein 1 (HP1). In turn, HP1 recruits or binds a plethora proteins, many with known roles in establishment function. Yet our knowledge about how these different partners assemble limited. Here we show that interactors engage Drosophila (HP1a) dimer through degenerate expanded form previously identified PxVxL motif, which now term HP1a Access Codes (HACs)....
Abstract We recently developed Di rected Me thylation with Lo ng-read seq uencing (DiMeLo-seq) to map protein-DNA interactions genome wide. DiMeLo-seq is capable of mapping multiple interaction sites on single DNA molecules, profiling protein binding in the context endogenous methylation, identifying haplotype specific interactions, and repetitive regions that are difficult study short-read methods. With DiMeLo-seq, adenines vicinity a interest methylated situ by tethering Hia5...
Returns, and: House on the Coast Road Lucy Brennan (bio) Returns Behind plum tree, pushing its way througha screen of cultivated, flowering shrubs,a common briar I'd cut right down to nubshad sprouted out in spring, crisp-thorned and blue. I went picking berries here todayand slipped back Septembers after school,scrambling about hedges, chafed by rulesafter long days summer loose reins. Then was single-minded intensein stark innocence concentration:gathering fruit, tonguing sharp...