Conserved as well as divergent regulatory elements account for expression of the human and rodent phenylalanine hydroxylase genes.
Gene
; 274(1-2): 283-91, 2001 Aug 22.
Article
en En
| MEDLINE
| ID: mdl-11675021
ABSTRACT
We have uncovered a fundamental difference in the regulation of the rodent and the human phenylalanine hydroxylase (PAH) genes expression of human PAH is independent of glucocorticoids and/or cAMP in contrast to the mouse gene which is not only highly inducible but dependent upon hormones for expression. Nevertheless, the two genes do exhibit similarities DNaseI hypersensitive sites are identically located in the regulatory regions, and the sequences around these sites are partially conserved and associated with regulatory elements sharing similar function. In transient transfections, the human proximal promoter is tissue-specific and presents significant activity compared to the extremely low and ubiquitous activity of the mouse promoter. DNA fragments corresponding to the two upstream hypersensitive sites of both genes have enhancer activity that depends upon the liver-enriched transcription factor binding sites for hepatocyte nuclear factor (HNF) 1 and/or CCAAT/enhancer binding protein (C/EBP). While expression of the rodent gene relies upon two modules in the HSIII enhancer, one activated by HNF1 and C/EBP and the other required for the hormone response, the human equivalent has conserved only the liver-specific transcription factor binding module. Even though the more proximal enhancer is not necessary for full reporter gene activity in transient transfection assays in Pah-expressing hepatoma cells, this enhancer could be required in both species for activation during development.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenilalanina Hidroxilasa
/
Proteínas Nucleares
/
Secuencias Reguladoras de Ácidos Nucleicos
/
Proteínas de Unión al ADN
Idioma:
En
Revista:
Gene
Año:
2001
Tipo del documento:
Article
País de afiliación:
Francia