Evaluating a Model of an NRE Mediated Tissue-Specific Expression of Murine Renin Genes.
-We have used comparative sequence analysis to evaluate a putative silencer element that has been proposed to be involved in the differential tissue-expression of the murine renin genes: Ren-1 and Ren-2. In the mouse, these genes share a similar pattern of tissue-specific renin expression. One significant difference is seen in the submandibular gland (SMG) where renin expression from the Ren-2 locus is 100-fold greater than the expression from the Ren-1 locus. One model proposes that this differential expression arises from the interplay among a negative regulatory element and a cAMP responsive element, their respective binding factors, and the disruption of the negative regulatory element by an insertion (M2) that is found in Ren-2 but not in Ren-1. The abrogation of the negative regulatory element's function as a result of the M2 insertion was proposed to be specifically responsible for the higher level of Ren-2 expression in the SMG as compared with Ren-1. We have assessed this hypothesis by looking at an allelic variant in the closely related mouse species M. hortulanus. This species shares the same high level of Ren-2 expression in the SMG as seen in other Ren-2 positive mouse strains. However, the Ren-2 M. hortulanus allele does not appear to contain the disruptive M2 element according to restriction-enzyme mapping. Our sequence analysis confirms that the M. hortulanus Ren-2 allele contains the same sequence elements present in the DBA/2 Ren-2 allele except for the M2 element. Moreover, the proposed negative regulatory element is intact at the sequence level in Ren-2 M. hortulanus allele. This analysis suggests that any involvement of the negative regulatory element in differential Ren-1 and Ren-2 expression in the SMG is not as straightforward as previously hypothesized.
Abonia
J. Pablo
JP
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute (J.P.A., T.A.B., C.A.J., K.W.G.), Buffalo, NY.
Howles
Philip N.
PN
Abel
Kenneth J.
KJ
Black
Thomas A.
TA
Jones
Craig A.
CA
Gross
Kenneth W.
KW