STRUCTURE, SEQUENCE, AND CHROMOSOME-19 LOCALIZATION OF HUMAN USF2 ANDITS REARRANGEMENT IN A PATIENT WITH MULTICYSTIC RENAL DYSPLASIA

The precise etiology of hydronephrosis caused by pelvi-ureteric juncti on obstruction is not yet known but there is convincing evidence for a genetic cause, with linkage analysis predicting a hereditary hydronep hrosis locus on chromosome 6p. In previous studies, a patient was desc ribed with a de novo autosomal t(6;19)(p21;q13.1) translocation and su ffering from bilateral multicystic renal dysplasia (MRD) caused by a b ilateral complete pelvi-ureteric junction obstruction, In an effort to elucidate a possible correlation between this translocation and hered itary hydronephrosis, we have carried out an extensive molecular chara cterization of a chromosome 19 cosmid clone previously identified as s panning the translocation in this unique index case. DNA sequencing ac ross a 9.2-kb BamHI fragment that straddles the translocation indicate s the presence of DNA sequences with a high degree of similarity to th e USF2 gene that encodes the transcription factor USF2 (upstream stimu lator factor 2). The genomic structure of USF2 consists of 10 exons di stributed over a DNA region of about 11 kb. The putative promoter regi on is CC-rich and lacks TATA and CCAAT boxes, suggesting that expressi on of the USF2 gene may be controlled by a typical housekeeping gene p romoter. The chromosome 19 breakpoint in the MRD patient appeared to h ave occurred in intron 7 of the USF2 gene. Northern blot analysis of a variety of human tissues revealed that the USF2 gene is ubiquitously expressed. Furthermore, Northern blot and 3'-RACE analysis of mRNA iso lated from lung fibroblasts of the MRD patient failed to detect a fusi on transcript involving USF2 sequences, suggesting gene disruption rat her than the generation of a fusion gene as a possible underlying mech anism. (C) 1996 Academic Press, Inc.