Centromere assembly and propagation is governed by genetic and epigenetic mechanisms. A centromere-specific histone H3 variant, CENP-A is strongly favored as the epigenetic mark that specifies centromere identity. Despite the critical importance of centromere function, centromeric sequences are not conserved. This has prompted exploration of other genomic and chromatin features to gain an understanding of where CENP-A is deposited. In this review we highlight recent papers that advance our understanding of how the cell builds a centromere. We focus on what influences the choice of site for CENP-A deposition and therefore the site of centromere formation. We then briefly discuss how centromeres are propagated once the site of centromere assembly is chosen.
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