Untitled

Abstract

Activation of transcription within chromatin has been correlated with the incorporation of the essential histone variant H2A.Z into nucleosomes. H2A.Z and other histone variants may establish structurally distinct chromosomal domains; however, the molecular mechanism by which they function is largely unknown. Here we report the 2.6 A crystal structure of a nucleosome core particle containing the histone variant H2A.Z. The overall structure is similar to that of the previously reported 2.8 A nucleosome structure containing major histone proteins. However, distinct localized changes result in the subtle destabilization of the interaction between the (H2A.Z-H2B) dimer and the (H3-H4)(2) tetramer. Moreover, H2A.Z nucleosomes have an altered surface that includes a metal ion. This altered surface may lead to changes in higher order structure, and/or could result in the association of specific nuclear proteins with H2A.Z. Finally, incorporation of H2A.Z and H2A within the same nucleosome is unlikely, due to significant changes in the interface between the two H2A.Z-H2B dimers.

Variant Histone H2A.Z Is Globally Localized to the Promoters of Inactive Yeast Genes and Regulates Nucleosome Positioning

“…Because the average size of the DNA fragments used in our ChIP assays is 400 bp, this suggests that most 400-bp fragments within the genome that contains H2A.Z will also contain H2A. Since, in principle, a nucleosome cannot contain both H2A and H2A.Z simultaneously [35], the data suggest that H2A.Z occupies regions that are smaller than 400 bp. Second, the size of the Z loci as they appear from the microarray data (see Figure 1, for example) are consistent with H2A.Z occupying small regions—especially considering the fact that ChIP experiments necessarily overestimate the size of the region bound by proteins due to the size of the chromatin fragments generated.…”

Nucleosome adaptability conferred by sequence and structural variations in histone H2A–H2B dimers

“…The atomic-resolution X-ray structures of variant nucleosomes are available for H2A.Z [36,37] and mH2A (histone domain) [38,39] variants, their structural superposition with canonical histones shows very similar conformations with the exception of the L1-loop regions of H2A (Figure 3a). In fact, this is the only region where the two H2A-H2B dimers interact.…”

Chromatin remodelling beyond transcription: the INO80 and SWR1 complexes

“…Analyses of chromatin fibres in vitro suggest that H2AZ promotes different conformational states of the nucleosome that might facilitate varied chromatin functions 44 . Specifically, the crystal structure of H2AZ-containing nucleosomes suggests that the nucleosome is destabilized by a region that includes the carboxyl-terminal α-helix of H2AZ, which contains a high degree of sequence divergence from H2A 45 (BOX 1). Loss of this H2AZ C-terminal region results in poor survival in yeast 27 and impaired development in D. melanogaster 46 .…”