Acquisition and Metastability of Centromere Identity and Function: Sequence Analysis of a Human Neocentromere
- MBVL, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037 USA
This extract was created in the absence of an abstract.
In this issue, Barry and colleagues (Barry et al. 2000) report the sequence of an 80 kb region of euchromatin from human chromosome 10 that can acquire centromeric activity. This new centromere, or neocentromere, drives stable mitotic inheritance once established. Approximately 40 neocentromeres have so far been identified in humans (Warburton et al. 2000). Patients with such neocentromere-containing rearranged chromosomes are heterozygous for the chromosome aberration [marker deletion, or mardel(10)], and so contain homologous loci that are independently inert or fully functional for centromere activity (Voullaire et al. 1993). This study completes a sequence analysis of the neocentromere region (Barry et al. 1999) and investigates what sequence polymorphisms, if any, occur when acquiring neocentromeric activity (Barry and colleagues 2000). We find no evidence for any sequence change, data that strongly support an epigenetic mechanism for neocentromere identity and regulation.
DNA associated with neocentromere activity in mardel(10) (NC DNA) was previously identified by examining the distribution of centromere proteins (primarily centromere proteins CENPs A and C) on stretched chromosomes, relative to the location of regions identified by fluorescence in situ hybridization (du Sart et al. 1997). The restriction map of this 80 kb region of NC DNA was compared to that of homologous non-neocentromeric (HC) DNA from a non-parental source, which demonstrated that no substantial polymorphisms exist between the neocentromere and wild-type genomic library clones (Barry et al. 1999). However, these results are open to the caveat that small changes in primary DNA structure can be causative in centromeric activity, and that these changes are below the resolution of restriction mapping.
Additionally, the entire NC sequence had been determined and analyzed for motifs or presence of repeat DNAs, some of which have been weakly correlated with centromeric activity. The NC sequence was not significantly different from random sequence in regard to …
