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Epigenetic dynamics of centromeres and neocentromeres in Cryptococcus deuterogattii.

Publication ,  Journal Article
Schotanus, K; Yadav, V; Heitman, J
Published in: PLoS Genet
August 2021

Deletion of native centromeres in the human fungal pathogen Cryptococcus deuterogattii leads to neocentromere formation. Native centromeres span truncated transposable elements, while neocentromeres do not and instead span actively expressed genes. To explore the epigenetic organization of neocentromeres, we analyzed the distribution of the heterochromatic histone modification H3K9me2, 5mC DNA methylation and the euchromatin mark H3K4me2. Native centromeres are enriched for both H3K9me2 and 5mC DNA methylation marks and are devoid of H3K4me2, while neocentromeres do not exhibit any of these features. Neocentromeres in cen10Δ mutants are unstable and chromosome-chromosome fusions occur. After chromosome fusion, the neocentromere is inactivated and the native centromere of the chromosome fusion partner remains as the sole, active centromere. In the present study, the active centromere of a fused chromosome was deleted to investigate if epigenetic memory promoted the re-activation of the inactive neocentromere. Our results show that the inactive neocentromere is not re-activated and instead a novel neocentromere forms directly adjacent to the deleted centromere of the fused chromosome. To study the impact of transcription on centromere stability, the actively expressed URA5 gene was introduced into the CENP-A bound regions of a native centromere. The introduction of the URA5 gene led to a loss of CENP-A from the native centromere, and a neocentromere formed adjacent to the native centromere location. Remarkably, the inactive, native centromere remained enriched for heterochromatin, yet the integrated gene was expressed and devoid of H3K9me2. A cumulative analysis of multiple CENP-A distribution profiles revealed centromere drift in C. deuterogattii, a previously unreported phenomenon in fungi. The CENP-A-binding shifted within the ORF-free regions and showed a possible association with a truncated transposable element. Taken together, our findings reveal that neocentromeres in C. deuterogattii are highly unstable and are not marked with an epigenetic memory, distinguishing them from native centromeres.

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Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

August 2021

Volume

17

Issue

8

Start / End Page

e1009743

Location

United States

Related Subject Headings

  • Membrane Transport Proteins
  • Epigenomics
  • Epigenesis, Genetic
  • Developmental Biology
  • DNA Methylation
  • Cryptococcus
  • Chromosomal Proteins, Non-Histone
  • Chromatin
  • Centromere Protein A
  • Centromere
 

Citation

APA
Chicago
ICMJE
MLA
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Schotanus, K., Yadav, V., & Heitman, J. (2021). Epigenetic dynamics of centromeres and neocentromeres in Cryptococcus deuterogattii. PLoS Genet, 17(8), e1009743. https://doi.org/10.1371/journal.pgen.1009743
Schotanus, Klaas, Vikas Yadav, and Joseph Heitman. “Epigenetic dynamics of centromeres and neocentromeres in Cryptococcus deuterogattii.PLoS Genet 17, no. 8 (August 2021): e1009743. https://doi.org/10.1371/journal.pgen.1009743.
Schotanus K, Yadav V, Heitman J. Epigenetic dynamics of centromeres and neocentromeres in Cryptococcus deuterogattii. PLoS Genet. 2021 Aug;17(8):e1009743.
Schotanus, Klaas, et al. “Epigenetic dynamics of centromeres and neocentromeres in Cryptococcus deuterogattii.PLoS Genet, vol. 17, no. 8, Aug. 2021, p. e1009743. Pubmed, doi:10.1371/journal.pgen.1009743.
Schotanus K, Yadav V, Heitman J. Epigenetic dynamics of centromeres and neocentromeres in Cryptococcus deuterogattii. PLoS Genet. 2021 Aug;17(8):e1009743.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

August 2021

Volume

17

Issue

8

Start / End Page

e1009743

Location

United States

Related Subject Headings

  • Membrane Transport Proteins
  • Epigenomics
  • Epigenesis, Genetic
  • Developmental Biology
  • DNA Methylation
  • Cryptococcus
  • Chromosomal Proteins, Non-Histone
  • Chromatin
  • Centromere Protein A
  • Centromere