The formation of de novo centromeres on artificial chromosomes in humans (HACs) and fission yeast (SpYACs) has provided much insights to the epigenetic and genetic control on regional centromere establishment and maintenance. Similarly, the use of artificial chromosomes in point centromeric budding yeast Saccharomyces cerevisiae (ScYACs) and holocentric Caenorhabditis elegans (WACs) has revealed epigenetic regulation in the originally thought purely genetically-determined point centromeres and some centromeric DNA sequence features in holocentromeres, respectively. These relatively extreme and less characterized centromere organizations, on the endogenous chromosomes and artificial chromosomes, will be discussed and compared to the more well-studied regional centromere systems. This review will highlight some of the common epigenetic and genetic features in different centromere architectures, including the presence of the centromeric histone H3 variant, CENP-A or CenH3, centromeric and pericentric transcription, AT-richness and repetitiveness of centromeric DNA sequences.