NDLI: Determinants of Histone H4 N-terminal Domain Function during Nucleosomal Array Oligomerization

Content Provider	PubMed Central
Author	Mcbryant, Steven J. Klonoski, Joshua Sorensen, Troy C. Norskog, Sarah S. Williams, Sere Resch, Michael G. Toombs, James A. Hobdey, Sarah E. Hansen, Jeffrey C.
Abstract	Mg2+-dependent oligomerization of nucleosomal arrays is correlated with higher order folding transitions that stabilize chromosome structure beyond the 30-nm diameter fiber. In the present studies, we have employed a novel mutagenesis-based approach to identify the macromolecular determinants that control H4 N-terminal domain (NTD) function during oligomerization. Core histones were engineered in which 1) the H2A, H2B, and H3 NTDs were swapped onto the H4 histone fold; 2) the length of the H4 NTD and the H2A NTD on the H4 histone fold, were increased; 3) the charge density of the NTDs on the H4 histone fold was increased or decreased; and 4) the H4 NTD was placed on the H2B histone fold. Model nucleosomal arrays were assembled from wild type and mutant core histone octamers, and Mg2+-dependent oligomerization was characterized. The results demonstrated that the H2B and H3 NTDs could replace the H4 NTD, as could the H2A NTD if it was duplicated to the length of the native H4 NTD. Arrays oligomerized at lower salt concentrations as the length of the NTD on the H4 histone fold was increased. Mutations that decreased the NTD charge density required more Mg2+ to oligomerize, whereas mutants that increased the charge density required less salt. Finally, the H4 NTD functioned differently when attached to the H2B histone fold than the H4 histone fold. These studies have revealed new insights into the biochemical basis for H4 NTD effects on genome architecture as well as the protein chemistry that underlies the function of the intrinsically disordered H4 NTD.
Related Links	http://dx.doi.org/10.1074/jbc.M109.011288
Starting Page	16716
File Format	PDF
ISSN	1083351X
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	25
Volume Number	284
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2009-06-19
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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