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Each chromosome contains a centromere, the site at which the kinetochore assembles to ensure accurate chromosome segregation during cell division. Centromeric chromatin, which anchors the kinetochore, includes three core proteins: Centromere Protein A (CENP-A), CENP-B, and CENP-C. Among these, CENP-B is unique for its sequence-specific DNA binding to a 17-base pair element known as the CENP-B box within the alpha-satellite DNA. CENP-B contains an N-terminal DNA-binding domain and a C-terminal dimerization domain that together enable juxtaposition of distant CENP-B boxes and promote higher-order centromeric structure. CENP-B also interacts directly with CENP-A and CENP-C, thereby facilitating kinetochore assembly. The CENP-B box includes two CpG dinucleotides that, when methylated, reduce CENP-B binding and limit recruitment of CENP-A and CENP-C. The recently completed human genome assembly (T2T-CHM13) revealed centromeric regions with low CpG methylation, termed centromere dip regions, that coincide with active, unmethylated CENP-B boxes. The uniform density of these unmethylated sites across chromosomes contributes to balanced kinetochore-spindle attachment. The CENP-B gene shows no pathogenic alterations in the American Association for Cancer Research (AACR) GENIE cancer cohort (211,526 patients), underscoring its conserved role in chromosome stability.
Fritz F. Parl (Mon,) studied this question.