EWSR1 maintains centromere identity

Cell Rep. 2023 Jun 27;42(6):112568. doi: 10.1016/j.celrep.2023.112568. Epub 2023 May 25.


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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Autoantigens / metabolism
  • Centromere Protein A / genetics
  • Centromere* / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Humans
  • RNA
  • RNA-Binding Protein EWS* / genetics
  • RNA-Binding Protein EWS* / metabolism
  • Sarcoma, Ewing


  • Autoantigens
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • EWSR1 protein, human
  • RNA
  • RNA-Binding Protein EWS