THE MICROSATELLITE SEQUENCE (CT)(N).(GA)(N) PROMOTES STABLE CHROMOSOMAL INTEGRATION OF LARGE TANDEM ARRAYS OF FUNCTIONAL HUMAN U2 SMALL NUCLEAR-RNA GENES

The multigene family encoding human U2 small nuclear RNA (snRNA) is or ganized as a single large tandem array containing 5 to 25 copies of a 6.1-kb repeat unit (the RNU2 locus), Remarkably, each of the repeat un its within an individual U2 tandem array appears to he identical excep t for an irregular dinucleotide tract, known as the CT microsatellite, which exhibits minor length and sequence polymorphism, Using a somati c cell genetic assay, we previously noticed that the CT microsatellite appeared to stabilize artificial tandem arrays of U2 snRNA genes, We now demonstrate that the CT microsatellite is required to establish la rge tandem arrays of transcriptionally-active U2 genes, increasing bot h the average and maximum size of the resulting arrays, In contrast, t he CT microsatellite has no effect on the average or maximal size of a rtificial arrays containing transcriptionally inactive U2 genes that l ack key promotes elements, Our data reinforce the connection between r ecombination and transcription. Active U2 transcription interferes wit h establishment or maintenance of the U2 tandem array, and the CT micr osatellite opposes these effects, perhaps hy binding GAGA or GAGA-sela ted factors which alter local chromatin structure, We speculate that t he mechanisms responsible for maintenance of tandem arrays containing active promoters may differ from those that maintain tandem arrays of transcriptionally inactive sequences.