- Genomics and Chromatin Dynamics
- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Antifungal resistance and susceptibility
- Ubiquitin and proteasome pathways
- Chromosomal and Genetic Variations
- Fungal Infections and Studies
- Plant Molecular Biology Research
- Chromatin Remodeling and Cancer
- Histone Deacetylase Inhibitors Research
- Slime Mold and Myxomycetes Research
- Cancer-related gene regulation
- Plant Disease Resistance and Genetics
- Genetics, Bioinformatics, and Biomedical Research
- CRISPR and Genetic Engineering
- Peptidase Inhibition and Analysis
- Nutrition, Genetics, and Disease
- Diatoms and Algae Research
University of Rochester Medical Center
2015-2025
University of Rochester
2008-2023
University Medical Center
2016-2023
Cornell University
2017
Pennsylvania State University
2017
Centre National de la Recherche Scientifique
2010-2013
Milbank Memorial Fund
2011-2012
Université Claude Bernard Lyon 1
2010-2011
Laboratoire de Biologie et Modélisation de la Cellule
2010-2011
Université Grenoble Alpes
2010-2011
Exposure of Escherichia coli to a variety DNA‐damaging agents results in the induction global ‘SOS response’. Expression many genes SOS regulon are controlled by LexA protein. acts as transcriptional repressor these unlinked binding specific sequences (LexA boxes) located within promoter region each LexA‐regulated gene. Alignment 20 sites found E. chromosome reveals consensus 5′‐TACTG(TA) 5 CAGTA‐3′. DNA that exhibit close match said have low heterology index and bind tightly, whereas those...
We describe the application of hydroxyl radical footprinting technique to examine histone-DNA interactions a nucleosome that includes part 5S ribosomal RNA gene Xenopus borealis. establish two distinct regions DNA with different helical periodicities exist within and demonstrate change in periodicity this upon formation. In particular, we find on average is 10.18 +/- 0.05 base pairs per turn. The same DNA, when bound calcium phosphate surface, has 10.49 turn, similar random sequence DNA....
We describe the application of hydroxyl radical footprinting technique to examine contribution core histone tails and histones H3 H4 structure DNA in nucleosome. first establish that, as was previously determined for a nucleosome containing unique sequence DNA, mixed-sequence nucleosomes contain two distinct regions structure. The central three turns have helical periodicity approximately 10.7 base pairs per turn, while flanking 10.0 turn. Removal does not change cleavage pattern either...
Histone-DNA contacts within a nucleosome influence the function of trans-acting factors and molecular machines required to activate transcription process. The internal architecture positioned has now been probed with use photoactivatable cross-linking reagents determine placement histones along DNA molecule. A model for is proposed in which winged-helix domain linker histone asymmetrically located inside gyres that also wrap around core histones. This extends path protein superhelix one side...
Despite the key role of linker histone H1 in chromatin structure and dynamics, its location interactions with nucleosomal DNA have not been elucidated. In this work we used a combination electron cryomicroscopy, hydroxyl radical footprinting, nanoscale modeling to analyze precisely positioned mono-, di-, trinucleosomes containing physiologically assembled full-length or truncated mutants protein. Single-base resolution •OH footprinting shows that globular domain (GH1) interacts minor groove...
Nucleosome arrays undergo salt-dependent self-association into large oligomers in a process thought to recapitulate essential aspects of higher-order tertiary chromatin structure formation. Lysine acetylation within the core histone tail domains inhibits self-association, an effect likely related its role facilitating transcription. As specific may encode distinct functions, we investigated biochemical and properties model nucleosome containing combinations native mutant histones with...
The condensation of nucleosome arrays into higher-order secondary and tertiary chromatin structures likely involves long-range internucleosomal interactions mediated by the core histone tail domains. We have characterized interarray H4 domain, known to play a predominant role in formation such structures. find that N-terminal end mediates contacts with DNA during self-association oligonucleosome similar found previously for H3 domain. However, site near fold domain participates distinct set...
Femtosecond laser-induced surface structuring is a promising technique for the large-scale formation of nano- and microscale structures that can effectively modify materials' optical, electrical, mechanical, tribological properties. Here we perform systematic study on femtosecond gold (Au) their effect both hydrophobicity bacterial-adhesion We created various including subwavelength periodic (fs-LIPSSs), fs-LIPSSs covered with nano/microstructures, conic 1D-rod-like (≤ 6 μm), spherical...
We establish that linker histones H1 and H5 bind preferentially to a Xenopus borealis somatic 5S RNA gene associated with an octamer of core rather than naked DNA. This preferential binding requires free DNA either side the nucleosome core. Incorporation single histone molecule into protects additional 20 bp from micrococcal nuclease digestion. is asymmetrically distributed respect causes no change cleavage in by hydroxyl radical or DNase I.
The core histone tail domains are "master control switches" that help define the structural and functional characteristics of chromatin at many levels. tails modulate DNA accessibility within nucleosome, essential for stable folding oligonucleosome arrays into condensed fibers, important fiber-fiber interactions involved in higher order structures. Many nuclear signaling pathways impinge upon domains, resulting posttranslational modifications likely to alter charge, structure, and/or or...
We used a novel labeling technique in the naturally synchronous organism Physarum polycephalum to examine fate of core histones G2 phase. find rapid exchange H2A/H2B dimers with free pools that is greatly diminished by treatment cells α-amanitin. This enhanced pol II-coding sequences compared extragenic regions or inactive loci. In contrast, H3/H4 tetramers exhibit far lower levels II-transcribed genes tested, suggesting tetramer occurs via distinct mechanism. However, we transcribed...
A Xenopus borealis somatic 5S RNA gene was assembled with either the complete octamer of histones, (H2A/H2B/H3/H4)2, or (H3/H4)2 tetramer histones that comprises central protein kernel nucleosome. Gel-mobility shifts, DNase I protection, and immunoblotting assays demonstrate class III transcription factor IIIA (TFIIIA) readily interacts DNA associated but little no binding is detected when full histones. Thus, presence H2A H2B in nucleosome significantly inhibits interaction TFIIIA its...
The core histone tail domains play a central role in chromatin structure and epigenetic processes controlling gene expression. Although little is known regarding the molecular details of interactions, it likely that they participate both short-range long-range interactions between nucleosomes. Previously, we demonstrated H3 domain participates internucleosome during MgCl2-dependent condensation model nucleosome arrays. However, these studies did not distinguish whether represented...