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Chromatin remodelers Isw1 and Chd1 maintain chromatin structure during transcription by preventing histone exchange

Abstract

Set2-mediated methylation of histone H3 Lys36 (H3K36) is a mark associated with the coding sequences of actively transcribed genes, but it has a negative role during transcription elongation. It prevents trans-histone exchange over coding regions and signals for histone deacetylation in the wake of RNA polymerase II (RNAPII) passage. We have found that in Saccharomyces cerevisiae the Isw1b chromatin-remodeling complex is specifically recruited to open reading frames (ORFs) by H3K36 methylation through the PWWP domain of its Ioc4 subunit in vivo and in vitro. Isw1b acts in conjunction with Chd1 to regulate chromatin structure by preventing trans-histone exchange from taking place over coding regions. In this way, Isw1b and Chd1 are important in maintaining chromatin integrity during transcription elongation by RNAPII.

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Figure 1: Subunit composition and domain organization of Isw1 and Chd1 remodelers.
Figure 2: Ioc4 preferentially binds H3K36me3 nucleosomes.
Figure 3: Deletion of SET2 abrogates localization of Ioc4 to coding regions.
Figure 4: ISW1 and CHD1 have overlapping functions during transcription within the Set2 pathway.
Figure 5: Deletion of ISW1 and CHD1 causes widespread intragenic transcription.
Figure 6: Deletion of ISW1 and CHD1 increases histone exchange over 3′ ends of ORFs.
Figure 7: Deletion of ISW1 and CHD1 increases histone acetylation over coding regions.

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Acknowledgements

We thank O. Rando (University of Massachusetts Medical School) and T. Tsukiyama (Fred Hutchinson Cancer Research Center) for providing yeast strains, and members of the Workman lab for helpful discussions, including A. Dutta for technical advice on EMSA and V. Weake for critical reading of the manuscript. This work was supported by US National Institutes of Health (NIH) grant R01GM047867 to J.L.W. and the Stowers Institute for Medical Research.

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M.S. designed and carried out experiments, analyzed the data and wrote the manuscript. M.S., M.M.G., S.V. and H.L. carried out bioinformatics analyses. Y.Z., L.F. and M.P.W. performed MS and analyzed the results. J.L.W. supervised experiments and wrote the manuscript.

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Correspondence to Jerry L Workman.

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The authors declare no competing financial interests.

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Smolle, M., Venkatesh, S., Gogol, M. et al. Chromatin remodelers Isw1 and Chd1 maintain chromatin structure during transcription by preventing histone exchange. Nat Struct Mol Biol 19, 884–892 (2012). https://doi.org/10.1038/nsmb.2312

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