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The SIN domain of the histone octamer is essential for intramolecular folding of nucleosomal arrays

Abstract

The SIN domain within histones H3 and H4 is defined by a set of single amino acid substitutions that were initially identified as mutations that alleviate the transcriptional defects associated with inactivation of the SWI/SNF chromatin remodeling complex. Here we use recombinant histones to investigate how Sin versions of H4 alter the structure of nucleosomal arrays. We find that an R45C substitution within the SIN domain of H4 does not disrupt nucleosome positioning nor does this Sin version alter the accessibility of nucleosomal DNA. In contrast, we find that the R45C substitution eliminates Mg2+-dependent, intramolecular folding of the nucleosomal arrays. Our results suggest that Sin versions of histones may alleviate the need for SWI/SNF in vivo by disrupting higher-order chromatin folding.

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Acknowledgements

We would like to thank K. Luger for assistance in preparation of recombinant histones and helpful advice throughout the course of these studies, and M. Shogren-Knaak and E. Merithew for help with the preparation of Fig. 4. These studies were supported by grants from the NIH to C.L.P. and J.C.H., and a NIH NRSA to P.J.H.

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The authors declare no competing financial interests.

Correspondence to Craig L. Peterson.

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Figure 1: Sin versions of histone H4 are competent to form nucleosomal arrays.
Figure 2: Sin versions of histone H4 abolish intramolecular folding of arrays.
Figure 3: SWI/SNF efficiently remodels both wild type and Sin arrays.
Figure 4: The SIN domain plays a key role in the organization of both the central and peripheral wraps of nucleosomal DNA.