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Phosphorylation of linker histones regulates ATP-dependent chromatin remodeling enzymes

Abstract

Members of the ATP-dependent family of chromatin remodeling enzymes play key roles in the regulation of transcription, development, DNA repair and cell cycle control. We find that the remodeling activities of the ySWI/SNF, hSWI/SNF, xMi-2 and xACF complexes are nearly abolished by incorporation of linker histones into nucleosomal array substrates. Much of this inhibition is independent of linker histone-induced folding of the arrays. We also find that phosphorylation of the linker histone by Cdc2/Cyclin B kinase can rescue remodeling by ySWI/SNF. These results suggest that linker histones exert a global, genome-wide control over remodeling activities, implicating a new, obligatory coupling between linker histone kinases and ATP-dependent remodeling enzymes.

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Figure 1: Linker histones inhibit SWI/SNF remodeling.
Figure 2: Linker histones do not prevent chromatin binding of ySWI/SNF.
Figure 3: Linker histones globally inhibit remodeling enzymes.
Figure 4: Linker histone phosphorylation rescues remodeling.

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Acknowledgements

These studies were supported by grants from the NIH to C.L.P. and J.C.H., a NIH NRSA to P.J.H, and a PO1 from the NCI to C.L.P. and A.N.I.

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Correspondence to Craig L. Peterson.

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The authors declare no competing financial interests.

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Horn, P., Carruthers, L., Logie, C. et al. Phosphorylation of linker histones regulates ATP-dependent chromatin remodeling enzymes. Nat Struct Mol Biol 9, 263–267 (2002). https://doi.org/10.1038/nsb776

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