The centromere is a key region for cell division where the kinetochore assembles, recognizes and attaches to microtubules so that each sister chromatid can segregate to each daughter cell. The centromeric chromatin is a unique rigid chromatin state promoted by the presence of the histone H3 variant CENP-A, in which epigenetic histone modifications of both heterochromatin or euchromatin states and associated protein elements are present. Although DNA sequence is not regarded as important for the establishment of centromere chromatin, it has become clear that this structure is formed as a result of a highly regulated epigenetic event that leads to the recruitment and stability of kinetochore proteins. We describe an integrative model for epigenetic processes that conform regional chromatin interactions indispensable for the recruitment and stability of kinetochore proteins. If alterations of these chromatin regions occur, chromosomal instability is promoted, although segregation may still take place.