CENPAcontaining

CENPAcontaining nucleosomes are centromeric chromatin particles in which the conventional histone H3 is replaced by the histone variant CENP-A. This substitution creates a specialized chromatin domain that helps define centromere identity and anchors the assembly of the kinetochore, the protein structure that mediates chromosome segregation during cell division.

The presence of CENP-A at centromeres acts as an epigenetic mark that is largely independent of the underlying DNA sequence. It promotes recruitment and stabilization of the constitutive centromere-associated network (CCAN) and kinetochore components, including CENP-C and CENP-N, which in turn connect centromeric chromatin to outer kinetochore microtubule attachment sites.

Deposition and maintenance of CENPAcontaining chromatin are tightly regulated. In human cells, the HJURP chaperone deposits new CENP-A at centromeres, with licensing factors such as the Mis18 complex ensuring proper timing and localization. Deposition generally occurs during late mitosis and early G1, while maintenance requires ongoing replenishment of CENP-A as cells divide, helping preserve centromere identity through generations.

structurally, CENP-A differs from canonical H3 in regions that influence nucleosome stability and chromatin architecture, contributing to a distinct chromatin state at the centromere. Although centromeric DNA sequences vary across species, the presence of CENP-A–containing nucleosomes is a common feature that supports robust kinetochore formation.

Mislocalization or depletion of CENP-A impairs centromere function and leads to chromosome missegregation and aneuploidy. Overexpression or abnormal regulation of CENP-A has been associated with chromosomal instability in certain cancers, highlighting its essential role in genome integrity.