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The N-terminal Tail of CENP-A Confers Epigenetic Stability to Centromeres via the CENP-T Branch of the CCAN in Fission Yeast


ABSTRACT: We employ the well-studied fission yeast centromere to investigate the function of the CENP-A (Cnp1) N-tail. We show that alteration of the N-tail did not affect Cnp1 loading at centromeres, outer kinetochore formation, or spindle checkpoint signaling, but nevertheless elevated chromosome loss. N-Tail mutants exhibited synthetic lethality with an altered centromeric DNA sequence, with rare survivors harboring chromosomal fusions in which the altered centromere was epigenetically inactivated. Elevated centromere inactivation was also observed for N-tail mutants with unaltered centromeric DNA sequences. N-tail mutants specifically reduced localization of the CCAN proteins Cnp20/CENP-T and Mis6/CENP-I, but not Cnp3/CENP-C. Overexpression of Cnp20/CENP-T suppressed defects in an N-tail mutant, suggesting a causal link between reduced CENP-T recruitment and the observed centromere inactivation phenotype. Thus, the Cnp1 N-tail promotes epigenetic stability of centromeres via recruitment of the CENP-T branch of the CCAN. Genome-wide localization of GFP-tagged N-tail Cnp1 variant tailswap versus wt control in cnp1 deletion background

ORGANISM(S): Schizosaccharomyces pombe

SUBMITTER: Arshad Desai 

PROVIDER: E-GEOD-63350 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The CENP-A N-tail confers epigenetic stability to centromeres via the CENP-T branch of the CCAN in fission yeast.

Folco H Diego HD   Campbell Christopher S CS   May Karen M KM   Espinoza Celso A CA   Oegema Karen K   Hardwick Kevin G KG   Grewal Shiv I S SIS   Desai Arshad A  

Current biology : CB 20150122 3


In most eukaryotes, centromeres are defined epigenetically by presence of the histone H3 variant CENP-A [1-3]. CENP-A-containing chromatin recruits the constitutive centromere-associated network (CCAN) of proteins, which in turn directs assembly of the outer kinetochore to form microtubule attachments and ensure chromosome segregation fidelity [4-6]. Whereas the mechanisms that load CENP-A at centromeres are being elucidated, the functions of its divergent N-terminal tail remain enigmatic [7-12]  ...[more]

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