EWSR1 maintains centromere identity

Risa Kitagawa, Yohei Niikura, Argentina Becker, Peter J. Houghton, Katsumi Kitagawa

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The centromere is essential for ensuring high-fidelity transmission of chromosomes. CENP-A, the centromeric histone H3 variant, is thought to be the epigenetic mark of centromere identity. CENP-A deposition at the centromere is crucial for proper centromere function and inheritance. Despite its importance, the precise mechanism responsible for maintenance of centromere position remains obscure. Here, we report a mechanism to maintain centromere identity. We demonstrate that CENP-A interacts with EWSR1 (Ewing sarcoma breakpoint region 1) and EWSR1-FLI1 (the oncogenic fusion protein in Ewing sarcoma). EWSR1 is required for maintaining CENP-A at the centromere in interphase cells. EWSR1 and EWSR1-FLI1 bind CENP-A through the SYGQ2 region within the prion-like domain, important for phase separation. EWSR1 binds to R-loops through its RNA-recognition motif in vitro. Both the domain and motif are required for maintaining CENP-A at the centromere. Therefore, we conclude that EWSR1 guards CENP-A in centromeric chromatins by binding to centromeric RNA.

Original languageEnglish (US)
Article number112568
JournalCell Reports
Volume42
Issue number6
DOIs
StatePublished - Jun 27 2023

Keywords

  • CENP-A
  • CENP-A maintenance
  • CP: Molecular biology
  • EWSR1
  • EWSR1-FLI1
  • Ewing sarcoma
  • Ewing sarcoma breakpoint region 1
  • Ewing sarcoma oncogenic fusion protein
  • centromere
  • centromere identity
  • kinetochore
  • phase separation

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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