M18BP1 valency and a distributed interaction footprint determine epigenetic centromere specification in humans

Area of Science:

• Cell Biology
• Epigenetics
• Molecular Biology

Background:

• Centromeres are crucial for chromosome segregation.
• CENP-A is an epigenetic mark defining centromeres.
• The assembly machinery for CENP-A deposition is not fully understood.

Purpose of the Study:

• To identify the localization determinants of M18BP1 at centromeres.
• To understand the role of M18BP1 dimerization in CENP-A deposition.
• To elucidate the mechanisms of centromere epigenetic inheritance.

Main Methods:

• Artificial M18BP1 dimerization in human cells.
• Structural analysis of the M18BP1 SANTA domain.
• Characterization of M18BP1 interactions with the CCAN.

Main Results:

• M18BP1 dimerization bypasses the need for MIS18α/β for centromere localization.
• Four determinants of M18BP1 centromere localization were identified, including the SANTA domain and linear motifs.
• M18BP1 dimerization is necessary and sufficient for its centromere localization.
• Cell-cycle-dependent M18BP1 dimerization facilitates CENP-A deposition.

Conclusions:

• M18BP1 dimerization is a critical step in CENP-A epigenetic inheritance.
• The identified M18BP1 determinants provide insights into centromere assembly.
• This study clarifies the molecular mechanisms underlying centromere identity maintenance.