H2A.Z contributes to the unique 3D structure of the centromere.
Mammalian centromere function depends upon a specialized chromatin organization where distinct domains of CENP-A and dimethyl K4 histone H3, forming centric chromatin, are uniquely positioned on or near the surface of the chromosome. These distinct domains are embedded in pericentric heterochromatin (characterized by H3 methylated at K9). The mechanisms that underpin this complex spatial organization are unknown. Here, we identify the essential histone variant H2A.Z as a new structural component of the centromere. Along linear chromatin fibers H2A.Z is distributed nonuniformly throughout heterochromatin, and centric chromatin where regions of nucleosomes containing H2A.Z and dimethylated K4 H3 are interspersed between subdomains of CENP-A. At metaphase, using the inactive X chromosome centromere as a model, complex folding of this fiber produces spatially positioned domains where H2A.Z/dimethylated K4 H3 chromatin juxtaposes one side of CENP-A chromatin, whereas a region of H2A/trimethyl K9 H3 borders the other side. A second region of H2A.Z is found, with trimethyl K9 H3 at the inner centromere. We therefore propose that H2A.Z plays an integral role in organizing centromere structure.
Greaves
Ian K
IK
The John Curtin School of Medical Research, Australian National University, P.O. Box 334, Canberra, The Australian Capital Territory 2601, Australia.
Rangasamy
Danny
D
Ridgway
Patricia
P
Tremethick
David J
DJ
D000818:Animals; D001324:Autoantigens / Q000737:chemistry; D002460:Cell Line; D002503:Centromere / Q000737:chemistry* / Q000648:ultrastructure*; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry; D041321:Chromosomes, Human, X / Q000737:chemistry / Q000648:ultrastructure; D004276:DNA, Satellite / Q000737:chemistry; D006570:Heterochromatin / Q000737:chemistry / Q000648:ultrastructure; D006657:Histones / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D049951:X Chromosome Inactivation
D001324:Autoantigens; C000619700:CENPA protein, human; C000619701:Cenpa protein, mouse; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D004276:DNA, Satellite; D006570:Heterochromatin; D006657:Histones