RT Journal Article
SR Electronic
T1 Swr1 mediated H2A.Z<sup>Pht1</sup> incorporation designates centromere DNA for <em>de novo</em> CENP-A<sup>Cnp1</sup> assembly
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 215962
DO 10.1101/215962
A1 Kulasegaran-Shylini, Raghavendran
A1 Subramanian, Lakxmi
A1 Kerr, Alastair R. W.
A1 Spanos, Christos
A1 Rappsilber, Juri
A1 Allshire, Robin C.
YR 2017
UL http://biorxiv.org/content/early/2017/11/08/215962.abstract
AB The underlying hallmark of centromeres is the presence of specialized nucleosomes in which histone H3 is replaced by CENP-A. The events that mediate the installation of CENP-A in place of H3 remain poorly characterized. H2A.Z is linked to transcriptional competence and associates with mammalian centromeres. We find that H2A.ZPht1 and the Swr1 complex are enriched in fission yeast CENP-ACnp1 chromatin. Our analysis shows that Swr1, Msc1 and H2A.ZPht1 are required to maintain CENP-ACnp1 chromatin integrity. Cell cycle analyses demonstrate that H2A.ZPht1 is deposited in S phase, coincident with the deposition of placeholder H3, and prior to CENP-ACnp1 replenishment in G2. Establishment assays reveal that H2A.ZPht1 and Swr1 are required for de novo assembly of CENP-ACnp1 onto naïve centromere DNA. We propose that features akin to promoters within centromere DNA program the incorporation of H2A.ZPht1 via Swr1, and mediate the replacement of resident H3 nucleosomes with CENP-A nucleosomes thereby defining centromeres.