Induction of myelin protein zero by early growth response 2 through upstream and intragenic elements.
J Biol Chem
; 284(30): 20111-20, 2009 Jul 24.
Article
em En
| MEDLINE
| ID: mdl-19487693
ABSTRACT
The Mpz (myelin protein zero) gene codes for the principal component of myelin in the peripheral nervous system, and mutations in this gene cause human peripheral myelinopathies. Expression of the Mpz gene is controlled by two major transactivators that coordinate Schwann cell development Egr2/Krox20 and Sox10. Our in vivo ChIP-chip analysis in myelinating peripheral nerve identified major sites of Egr2 interaction within the first intron of the Mpz gene and approximately 5 kb upstream of the transcription start site. In addition, the sites of Egr2 binding display many of the hallmarks associated with enhancer elements. Interestingly, the upstream Egr2 binding sites lie proximal to the divergently transcribed succinate dehydrogenase C gene, but Sdhc expression was not affected by the massive induction of Mpz mediated by Egr2. Mpz induction was greatly enhanced in the presence of the Egr2 binding sites, and removal of them markedly diminished transgenic expression of a construct derived from the Mpz locus. Sox10 was also found to be associated with the upstream region, and its binding was required for Egr2-mediated activation in this distal regulatory region. Our findings highlight that peripheral nerve-specific expression of Mpz is primarily regulated by both upstream and intron-associated regulatory elements. Overall, these results provide a locus-wide analysis of the role and activity of Egr2 in regulation of the Mpz gene within its native chromosomal context.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
/
Proteína P0 da Mielina
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Proteína 2 de Resposta de Crescimento Precoce
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos