The assay for unfolding used here has been used with transcriptional activators. It involves targeting BRCA1 or a subset of the protein to multiple (probably several thousand) lacO repeats scattered over 90 Mb of heterochromatin. In 14% of cells expressing BRCA1 linked to the lac repressor there is decondensation of this focused spot of DNA. Either BRCT1 or BRCT2 alone cause an even greater extent of decondensation in a higher percentage of cells (60%), although a construct containing both BRCT repeats has no effect. This suggests that the intact protein may be inhibited for chromatin unfolding, either by the binding of another protein or because of an intramolecular interaction that is relieved by another protein.

A candidate for that other factor is COBRA1, which Ye et al. isolate as a protein that interacts with BRCT1. COBRA1 by itself can mediate chromosome decondensation. A subset of...

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