Cell Reports: EWSR1 Maintains Centromere Identity (Kitagawa & Houghton labs)


  • EWSR1 is required to maintain CENP-A at the centromere in interphase cells
  • EWSR1 binds to CENP-A through the SYGQ2 region, important for phase separation
  • EWSR1 binds to R loops in vitro through its RNA-recognition motif (RRM)
  • EWSR1 protects CENP-A in the centromeric chromatin by binding to centromeric RNAs


The centromere is essential for ensuring the 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 the maintenance of the 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, which is 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.

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Article Categories: IF 10+, Research Paper