Dissertation
The Role of Linker DNA in Chromatin Fibers
The genetic information of all living organisms is contained in their DNA. Cells modify the degree of DNA compaction by epigenetics, which largely determines what genes are read out and which genes are transcriptionally silent.
- Author
- Brouwer, T.B.
- Date
- 04 November 2020
- Links
- Thesis in Leiden Repository
The genetic information of all living organisms is contained in their DNA. Cells modify the degree of DNA compaction by epigenetics, which largely determines what genes are read out and which genes are transcriptionally silent. Despite decades of research into this mechanism, there is no consensus on how cells realize the various degrees of DNA compaction in vivo. Eukaryotes, such as humans, compact their DNA into higher-order structures called compact chromatin fibers. We characterize these fibers through a combination of single-molecule force spectroscopy techniques like magnetic tweezers, and rigid base pair Monte Carlo simulations. We show that, for instance, the length and sequence of the linker DNA, the DNA between adjacent nucleosomes, control the mechanical properties of chromatin fibers. Our measurements suggest the formation of more than one higher-order fiber structure. A deeper understanding of the chromatin fiber and its compaction mechanism is important because the dysfunction of such regulation results in various medical conditions such as the epigenetic disorder type 1 diabetes, fragile X syndrome, or various cancers.