machinery during heterochromatin formation [14]. In the neocentromere on Chromosome 10 the heterochromatin proteinHP1doesnot co-localizewiththeCENPA-containing nucleosomes. The predominant positions that affect variegation of transgene expression inmice are pericentric heterochromatin, but chromosome engineering

Conclusions What practical relevance does this have? Manipulated or artificial chromosomes have been produced in several laboratories with the aim, at least in part, of providing an expression platform for genes that avoids both integration into host-cell genomes and position effects. Paradoxically, a potential problemwith this approach is that genes placed in close proximity to a centromere might be silenced by centromeric heterochromatin, but this now seems less of a concern. A better understanding of the requirements of a centromere in terms of formation, propagation and function in cell division is needed to produce better artificial chromosomes. The approaches discussed here that are used to define molecular markers of centromeric DNA, coupled with biochemistry and biophysics of centromeric chromatin, are a part of that process.