A NOVEL FAMILY OF REPEAT SEQUENCES IN THE MOUSE GENOME RESPONSIVE TO RETINOIC ACID

Repetitive DNA sequences form a substantial portion of eukaryotic geno mes and exist as members of families that differ in copy number, lengt h, and sequence. Various functions, including chromosomal integrity, g ene regulation, and gene rearrangement have been ascribed to repetitiv e DNA. Although there is evidence that some repetitive sequences may p articipate in gene regulation, little is known about how their own exp ression may be regulated. During the course of gene trapping experimen ts with embryonic stem (ES) cells, we identified a novel class of expr essed repetitive sequences in the mouse, using 5' rapid amplification of cDNA ends-polymerase chain reaction (5' RACE-PCR) to clone fusion t ranscripts from these lines. The expression of these repeats was induc ed by retinoic acid (RA) in cultured ES cells examined by Northern blo t analyses. In vivo, their expression was spatially restricted in embr yos and in the adult brain as determined by RNA in situ hybridization. We designated this family of sequences as Dr (developmentally regulat ed) repeats. The members of the Dr family, identified by cDNA cloning and through database search, are highly similar in sequence and show p eculiar structural features. Our results suggest the expression of Dr- containing transcripts may be part of an ES cell differentiation progr am triggered by RA.