Structure, sequence, and chromosome 19 localization of human USF2 and its rearrangement in a patient with multicystic renal dysplasia.
The precise etiology of hydronephrosis caused by pelvi-ureteric junction obstruction is not yet known but there is convincing evidence for a genetic cause, with linkage analysis predicting a hereditary hydronephrosis locus on chromosome 6p. In previous studies, a patient was described with a de novo autosomal t(6;19)(p21;q13.1) translocation and suffering from bilateral multicystic renal dysplasia (MRD) caused by a bilateral complete pelvi-ureteric junction obstruction. In an effort to elucidate a possible correlation between this translocation and hereditary hydronephrosis, we have carried out an extensive molecular characterization of a chromosome 19 cosmid clone previously identified as spanning the translocation in this unique index case. DNA sequencing across a 9.2-kb BamHI fragment that straddles the translocation indicates the presence of DNA sequences with a high degree of similarity to the USF2 gene that encodes the transcription factor USF2 (upstream stimulator factor 2). The genomic structure of USF2 consists of 10 exons distributed over a DNA region of about 11 kb. The putative promoter region is GC-rich and lacks TATA and CCAAT boxes, suggesting that expression of the USF2 gene may be controlled by a typical housekeeping gene promoter. The chromosome 19 breakpoint in the MRD patient appeared to have 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 isolated from lung fibroblasts of the MRD patient failed to detect a fusion transcript involving USF2 sequences, suggesting gene disruption rather than the generation of a fusion gene as a possible underlying mechanism.
Groenen
P M
PM
Laboratory of Molecular Oncology, Center for Human Genetics, University of Leuven, Belgium.
Garcia
E
E
Debeer
P
P
Devriendt
K
K
Fryns
J P
JP
Van de Ven
W J
WJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D002888:Chromosomes, Human, Pair 19; D004247:DNA; D004268:DNA-Binding Proteins; D005260:Female; D015870:Gene Expression; D015321:Gene Rearrangement; D006801:Humans; D008969:Molecular Sequence Data; D007690:Polycystic Kidney Diseases / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; D014157:Transcription Factors; C497184:USF2 protein, human; D051720:Upstream Stimulatory Factors; D004247:DNA