TY - JOUR
T1 - Histone H2A.Z inheritance during the cell cycle and its impact on promoter organization and dynamics
AU - Nekrasov, Maxim
AU - Amrichova, Jana
AU - Parker, Brian J.
AU - Soboleva, Tatiana A.
AU - Jack, Cameron
AU - Williams, Rohan
AU - Huttley, Gavin A.
AU - Tremethick, David J.
PY - 2012/11
Y1 - 2012/11
N2 - Although it has been clearly established that well-positioned histone H2A.Z-containing nucleosomes flank the nucleosome-depleted region (NDR) at the transcriptional start site (TSS) of active mammalian genes, how this chromatin-based information is transmitted through the cell cycle is unknown. We show here that in mouse trophoblast stem cells, the amount of histone H2A.Z at promoters decreased during S phase, coinciding with homotypic (H2A.Z-H2A.Z) nucleosomes flanking the TSS becoming heterotypic (H2A.Z-H2A). To our surprise these nucleosomes remained heterotypic at M phase. At the TSS, we identified an unstable heterotypic histone H2A.Z-containing nucleosome in G1 phase that was lost after DNA replication. These dynamic changes at the TSS mirror a global expansion of the NDR at S and M phases, which, unexpectedly, is unrelated to transcriptional activity. Coincident with the loss of histone H2A.Z at promoters, histone H2A.Z is targeted to the centromere when mitosis begins.
AB - Although it has been clearly established that well-positioned histone H2A.Z-containing nucleosomes flank the nucleosome-depleted region (NDR) at the transcriptional start site (TSS) of active mammalian genes, how this chromatin-based information is transmitted through the cell cycle is unknown. We show here that in mouse trophoblast stem cells, the amount of histone H2A.Z at promoters decreased during S phase, coinciding with homotypic (H2A.Z-H2A.Z) nucleosomes flanking the TSS becoming heterotypic (H2A.Z-H2A). To our surprise these nucleosomes remained heterotypic at M phase. At the TSS, we identified an unstable heterotypic histone H2A.Z-containing nucleosome in G1 phase that was lost after DNA replication. These dynamic changes at the TSS mirror a global expansion of the NDR at S and M phases, which, unexpectedly, is unrelated to transcriptional activity. Coincident with the loss of histone H2A.Z at promoters, histone H2A.Z is targeted to the centromere when mitosis begins.
UR - http://www.scopus.com/inward/record.url?scp=84869082555&partnerID=8YFLogxK
U2 - 10.1038/nsmb.2424
DO - 10.1038/nsmb.2424
M3 - Article
SN - 1545-9993
VL - 19
SP - 1076
EP - 1083
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 11
ER -