CBP and p300 are essential for renin cell identity and morphological integrity of the kidney.
The mechanisms that govern the identity of renin cells are not well understood. We and others have identified cAMP as an important pathway in the regulation of renin synthesis and release. Recently, experiments in cells from the renin lineage led us to propose that acquisition and maintenance of renin cell identity are mediated by cAMP and histone acetylation at the cAMP responsive element (CRE) of the renin gene. Ultimately, the transcriptional effects of cAMP depend on binding of the appropriate transcription factors to CRE. It has been suggested that access of transcription factors to this region of the promoter is facilitated by the coactivators CREB-binding protein (CBP) and p300, which possess histone acetyltransferase activity and may be, in turn, responsible for the remodeling of chromatin underlying expression of the renin gene. We hypothesized that CBP and p300 are therefore required for expression of the renin gene and maintenance of the renin cell. Because mice homozygous for the deletion of CBP or p300 die before kidney organogenesis begins, no data on kidney or juxtaglomerular cell development in these mice are available. Therefore, to define the role of these histone acetyltransferases in renin cell identity in vivo, we used a conditional deletion approach, in which floxed CBP and p300 mice were crossed with mice expressing cre recombinase in renin cells. Results show that the histone acetyltransferases CBP and p300 are necessary for maintenance of renin cell identity and structural integrity of the kidney.
Gomez
R Ariel
RA
Dept. of Pediatrics, Univ. of Virginia School of Medicine, 409 Lane Rd., MR4 2001, Charlottesville, VA 22908, USA. rg@virginia.edu
Pentz
Ellen Steward
ES
Jin
Xuan
X
Cordaillat
Magali
M
Sequeira Lopez
Maria Luisa S
ML
D000818:Animals; D050882:CREB-Binding Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage; D000242:Cyclic AMP / Q000378:metabolism; D050881:E1A-Associated p300 Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D007606:Juxtaglomerular Apparatus / Q000201:enzymology; D007668:Kidney / Q000201:enzymology* / Q000254:growth & development / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D038081:Organogenesis; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
C473112:Ren2 protein, mouse; D000242:Cyclic AMP; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; C045073:Cre recombinase; D019426:Integrases; D012083:Renin