Constitutive centromere-associated network controls centromere drift in vertebrate cells

Area of Science:

• Cell Biology
• Epigenetics
• Genomics

Background:

• Centromeres are crucial for chromosome segregation during cell division.
• Centromere specification is epigenetic and sequence-independent.
• The stability of centromere position over time is not well understood.

Purpose of the Study:

• To investigate the stability of centromere position in chicken DT40 cells.
• To determine if centromere position drifts during cell proliferation.
• To identify factors influencing centromere position stability.

Main Methods:

• Systematic analysis of nonrepetitive centromere positions in 21 independent cell clones.
• Chromatin immunoprecipitation combined with massive parallel sequencing (ChIP-seq) using anti-CENP-A antibody.
• Analysis of centromere position in subclones and in cells deficient for CENP-U and CENP-S.

Main Results:

• Centromere position varied significantly among independent clones, indicating centromere drift.
• Centromere position was relatively stable within subclones derived from a single clone.
• Centromere drift occurred more frequently in cells lacking CENP-U and CENP-S.

Conclusions:

• Centromere position can change over extended cell proliferation but is stable in short-term cultures.
• The complete centromere structure plays a role in suppressing centromere drift.
• Centromere proteins like CENP-U and CENP-S are involved in maintaining centromere position stability.