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Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Topological Polymorphism of Chromatin Fibers

Using computer simulations, we found two topologically distinct families of the chromatin fiber conformations distinguished by the linker length, L. The fibers with L = {10n} and {10n+5} bp have DNA linking numbers per nucleosome Lk ≈ –1.5 and –1.0, respectively (Norouzi and Zhurkin, 2015). The fibers with Lk ≈ –1.5 (T2) were observed earlier, while the topoisomer with Lk ≈ –1.0 (T1) is novel. These predictions were confirmed for circular nucleosome arrays with precisely positioned nucleosomes (Nikitina et al., 2017). We suggest that topological polymorphism of chromatin fibers may play a role in the process of transcription, i. e., the {10n+5} DNA linkers are likely to produce transcriptionally competent chromatin structures. This hypothesis is consistent with available data for several eukaryotes, from yeast to mouse (Norouzi et al., 2015; Norouzi and Zhurkin, 2018). Here, we analyzed the data from a recent genome-wide radio-probing study of DNA folding in human cells. The technique uses ionizing Radiation-Induced spatially Correlated Cleavage of DNA with sequencing (RICC-seq) to identify the DNA-DNA contacts that are spatially proximal (Risca et al., 2017). We show that the novel topoisomer with Lk ≈ –1.0 has to be taken into account to interpret the experimental data, especially for the transcriptionally active regions (Fig. 1). This is yet another evidence for occurrence of two distinct fiber topoisomers (Norouzi and Zhurkin, 2018). Potentially, our findings may reflect a general tendency of chromosomal domains with different levels of transcription to retain topologically distinct higher-order fiber conformations, T1 and T2.

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Figure 1. (Left) Comparison of the experimental RICC-seq data (Risca et al., 2017) with theoretical predictions (Norouzi and Zhurkin, 2018). The experimental genome-wide Fragment Length Distribution (FLD) profiles calculated for the transcriptionally active (H3K27ac, top red curve) and repressed (H3K9me3, top blue curve) regions in human genome correspond to the topoisomer T1 (bottom red curve) and T2 (bottom blue curve) respectively. (Center) Optimal folding of T1 and T2 are shown. (Right) The entry and the exit halves of nucleosomes (gyres) in the left stack are colored differently to emphasize distinct spatial organization of DNA in the T1 and T2 topoisomers, which results in different fragmentation patterns.

References

T. Nikitina, D. Norouzi, S. A. Grigoryev & V. B. Zhurkin. (2017). DNA topology in chromatin is defined by nucleosome spacing. Science Adv. 3:e1700957.

D. Norouzi & V. B. Zhurkin. (2015). Topological polymorphism of the two-start chromatin fiber. Biophys. J. 108, 2591-2600.

Norouzi D., and V. B. Zhurkin. (2018). Polymorphic 30-nm Chromatin Fiber and Linking Number Paradox. Evidence for the Occurrence of Two Distinct Topoisomers. bioRxiv 478396; doi: http://dx.doi.org/10.1101/478396.

D. Norouzi, A. Katebi, F. Cui & V. B. Zhurkin. (2015). Topological diversity of chromatin fibers: interplay between nucleosome repeat length, DNA linking number and the level of transcription. AIMS Biophys. 2, 613.

V. I. Risca, S. K. Denny, A. F. Straight & W. J. Greenleaf. (2017). Variable chromatin structure revealed by in situ spatially correlated DNA cleavage mapping. Nature 541, 237-241.

Davood Norouzi
Victor B. Zhurkin

Laboratory of Cell Biology
CCR
National Cancer Institute
NIH
Bethesda, MD 20892, USA

Email: zhurkin@nih.gov