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Intrinsic variability of gene expression encoded in nucleosome positioning sequences

Abstract

Variation in gene expression is an essential material for biological diversity among single cells1,2,3, individuals4,5,6 and populations or species7,8,9. Here we show that expression variability is an intrinsic property that persists at those different levels. Each promoter seems to have a unique capacity to respond to external signals that can be environmental, genetic or even stochastic. Our investigation into nucleosome organization of variably responding promoters revealed a commonly positioned nucleosome at a critical regulatory region where most transcription start sites and TATA elements are located, a deviation from typical nucleosome-free status. The nucleotide sequences in this region of variable promoters showed a high propensity for DNA bending and a periodic distribution of particular dinucleotides, encoding preferences for DNA–nucleosome interaction. Variable expression is likely to occur during removal of this nucleosome for gene activation. This is a unique example of how promoter sequences intrinsically encode regulatory flexibility, which is vital for biological processes such as adaptation, development and evolution.

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Figure 1: Interconnectedness of expression variability measures and chromatin regulation effect.
Figure 2: Variably expressed genes tend to possess a nucleosome at a specific position.
Figure 3: Positioning of stable nucleosomes in the promoters of variably expressed genes.
Figure 4: Nucleosome positioning of variably expressed genes determined by promoter sequences.

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Acknowledgements

This work was supported by grants from the Korean Ministry of Science and Technology to Y.-J.K. (Epigenomic Research of Human Disease and Global Research Lab).

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Correspondence to Young-Joon Kim.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1 and 2 and Supplementary Tables 2–4 (PDF 616 kb)

Supplementary Table 1

Variability measures, cre, and tre for each yeast gene (XLS 1337 kb)

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Choi, J., Kim, YJ. Intrinsic variability of gene expression encoded in nucleosome positioning sequences. Nat Genet 41, 498–503 (2009). https://doi.org/10.1038/ng.319

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