A nanoscale DNA force spectrometer capable of applying tension and compression on biomolecules.

Single molecule force spectroscopy is a powerful approach to probe the structure, conformational changes, and kinetic properties of biological and synthetic macromolecules. However, common approaches to apply forces to biomolecules require expensive and cumbersome equipment and relatively large probes such as beads or cantilevers, which limits their use for many environments and makes integrating with other methods challenging. Furthermore, existing methods have key limitations such as an inability to apply compressive forces on single molecules.

Quantitative Modeling of Nucleosome Unwrapping from Both Ends.

In eukaryotic cells, DNA is packaged into chromatin where nucleosomes are the basic packaging unit. Important cellular processes including gene expression, DNA replication, and DNA repair require nucleosomal DNA to be unwrapped so that functional proteins can access their target sites, which otherwise are sterically occluded. A key question in this process is what the unwrapped conformations individual nucleosomes adopt within chromatin are.

Covalent Modifications of Histone H3K9 Promote Binding of CHD3.

Chromatin remodeling is required for genome function and is facilitated by ATP-dependent complexes, such as nucleosome remodeling and deacetylase (NuRD). Among its core components is the chromodomain helicase DNA binding protein 3 (CHD3) whose functional significance is not well established. Here, we show that CHD3 co-localizes with the other NuRD subunits, including HDAC1, near the H3K9ac-enriched promoters of the NuRD target genes.

Probing Nucleosome Stability with a DNA Origami Nanocaliper.

The organization of eukaryotic DNA into nucleosomes and chromatin undergoes dynamic structural changes to regulate genome processing, including transcription and DNA repair. Critical chromatin rearrangements occur over a wide range of distances, including the mesoscopic length scale of tens of nanometers. However, there is a lack of methodologies that probe changes over this mesoscopic length scale within chromatin.