Since the discovery of the right-handed helical structure of DNA, 61 years have passed. The DNA molecule, which encodes genetic information, is also found twisted into coils. This extra twist of... Show moreSince the discovery of the right-handed helical structure of DNA, 61 years have passed. The DNA molecule, which encodes genetic information, is also found twisted into coils. This extra twist of the helical structure, called supercoiling, plays important roles in both DNA compaction and gene regulation. The DNA in eukaryotic cells is packaged into chromatin. Using single-molecule force spectroscopy, I resolved force/torque induced structural changes of DNA and chromatin fibers. I showed that the structural changes of chromatin fibers can be described by four conformations. I showed for the first time the folding and unfolding of a chromatin fiber under torsion. Th e anisotropic response of chromatin fibers to supercoiling reflects its leftŸ-handed chirality. These findings give a detailed structural insight of a supercoiled chromatin fiber, yielding a better understanding of the response of chromatin during transcription Show less
In eukaryotic cells, genomic DNA is organized in chromatin fibers composed of nucleosomes as structural units. A nucleosome contains 1.7 turns of DNA wrapped around a histone octamer and is... Show moreIn eukaryotic cells, genomic DNA is organized in chromatin fibers composed of nucleosomes as structural units. A nucleosome contains 1.7 turns of DNA wrapped around a histone octamer and is connected to the adjacent nucleosomes with linker DNA. The folding of chromatin fibers effectively increases the compaction of genomic DNA, but it remains accessible for enzymatic reactions. This apparent paradox motivates a detailed study of the dynamics of chromatin. A structural model at the molecular level will shed light on how cells regulate the compaction and dynamics of genomic DNA. This thesis presents the results of an experimental study on the dynamics of chromatin higher-order folding. Using magnetic tweezers, we observed force-dependent structural changes within chromatin fibers at the single nucleosome level. Show less