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Antagonistic forces that position nucleosomes in vivo

Abstract

ATP-dependent chromatin remodeling complexes are implicated in many areas of chromosome biology. However, the physiological role of many of these enzymes is still unclear. In budding yeast, the Isw2 complex slides nucleosomes along DNA. By analyzing the native chromatin structure of Isw2 targets, we have found that nucleosomes adopt default, DNA-directed positions when ISW2 is deleted. We provide evidence that Isw2 targets contain DNA sequences that are inhibitory to nucleosome formation and that these sequences facilitate the formation of nuclease-accessible open chromatin in the absence of Isw2. Our data show that the biological function of Isw2 is to position nucleosomes onto unfavorable DNA. These results reveal that antagonistic forces of Isw2 and the DNA sequence can control nucleosome positioning and genomic access in vivo.

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Figure 1: Isw2 repositions nucleosomes onto distinct DNA in vivo.
Figure 2: dA-dT DNA affects nucleosome positioning in vivo.
Figure 3: Control of nucleosome positioning and transcription at POT1.
Figure 4: Isw2 functions at the recombination enhancer.
Figure 5: Sequence elements common to Isw2 targets.
Figure 6: Model accounting for the interplay of Isw2 and unfavorable DNA.

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Acknowledgements

We thank members of the Tsukiyama, Biggins and Henikoff laboratories for helpful discussions; members of the Tsukiyama, Owen-Hughes and Hahn laboratories for critical reading of the manuscript; and G. Mizuguchi and C. Wu (National Cancer Institute, US National Institutes of Health) for the recombinant Drosophila histone octamer. This work was supported by US National Institutes of Health grant GM58465. T.T. is a Leukemia and Lymphoma Society Scholar.

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Correspondence to Toshio Tsukiyama.

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Supplementary information

Supplementary Fig. 1

DNA sequence of N1a variants (PDF 1428 kb)

Supplementary Fig. 2

Chromatin structure at POT1 in repressing and activating conditions (PDF 1777 kb)

Supplementary Fig. 3

Sequence characteristics and chromatin structure at the recombination enhancer (PDF 3321 kb)

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Whitehouse, I., Tsukiyama, T. Antagonistic forces that position nucleosomes in vivo. Nat Struct Mol Biol 13, 633–640 (2006). https://doi.org/10.1038/nsmb1111

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