EWSR1 maintains centromere identity.

Area of Science:

• Cell Biology
• Epigenetics
• Molecular Biology

Background:

• The centromere is crucial for accurate chromosome segregation during cell division.
• CENP-A, a histone H3 variant, is the epigenetic marker defining centromere identity.
• Mechanisms maintaining centromere identity and CENP-A localization are not fully understood.

Purpose of the Study:

• To elucidate the mechanism responsible for maintaining centromere identity.
• To investigate the role of EWSR1 in CENP-A localization and centromere function.

Main Methods:

• Investigated interactions between CENP-A and EWSR1.
• Assessed the requirement of EWSR1 for CENP-A maintenance in interphase cells.
• Analyzed binding domains (SYGQ2 region, RNA-recognition motif) of EWSR1 and EWSR1-FLI1 to CENP-A and R-loops.

Main Results:

• EWSR1 interacts with CENP-A and is essential for maintaining CENP-A at centromeres in interphase cells.
• EWSR1 and EWSR1-FLI1 bind CENP-A via the SYGQ2 region within the prion-like domain.
• EWSR1 binds to R-loops in vitro via its RNA-recognition motif.
• Both the SYGQ2 domain and RNA-recognition motif are necessary for maintaining CENP-A at the centromere.

Conclusions:

• EWSR1 acts as a guardian of centromeric chromatin by binding to centromeric RNA.
• This interaction is critical for maintaining CENP-A localization and centromere identity.
• The findings reveal a novel mechanism for centromere maintenance involving EWSR1 and RNA binding.