PreprintCited by 0Genomics and Chromatin DynamicsMicrotubule and mitosis dynamicsChromosomal and Genetic Variations

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Hap2-Ino80 facilitated transcription promotes de novo establishment of CENP-A chromatin

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Preprint — published as 10.1101/gad.332536.119

Abstract

SUMMARY: Centromeres are maintained epigenetically by the presence of CENP-A, an evolutionarily-conserved histone H3 variant, which directs kinetochore assembly and hence, centromere function. To identify factors that promote assembly of CENP-A chromatin, we affinity selected solubilised fission yeast CENP-A Cnp1 chromatin. All subunits of the Ino80 complex were enriched, including the auxiliary subunit Hap2. In addition to a role in maintenance of CENP-A Cnp1 chromatin integrity at endogenous centromeres, Hap2 is required for de novo assembly of CENP-A Cnp1 chromatin on naïve centromere DNA and promotes H3 turnover on centromere regions and other loci prone to CENP-A Cnp1 deposition. Prior to CENP-A Cnp1 chromatin assembly, Hap2 facilitates transcription from centromere DNA. These analyses suggest that Hap2-Ino80 destabilises H3 nucleosomes on centromere DNA through transcription-coupled histone H3 turnover, driving the replacement of resident H3 nucleosomes with CENP-A Cnp1 nucleosomes. These inherent properties define centromere DNA by directing a program that mediates CENP-A Cnp1 assembly on appropriate sequences.

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Metadata

Authors
Singh, P. P., Shukla, M., White, S. A., Tong, P., Auchynnikava, T., Spanos, C., Rappsilber, J., Pidoux, A. L., & Allshire, R. C.
Affiliations
Wellcome Centre for Cell Biology (GB)
Corresponding author
Allshire, Robin C.
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2019-09-23
OpenAlex
W2974105884
Cited by
0
References
1
Type
posted content
Language
en
Open access
Locations
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders
Darwin Trust of Edinburgh (103139)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
Keywords
CENP-A, Cnp1, centromere, HAP2, INO80 complex, centromere epigenetics, transcription, nucleosome destabilization, centromere DNA, kinetochore assembly, Schizosaccharomyces pombe, histone variant deposition

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