Sodium butyrate-mediated Sp3 acetylation represses human insulin-like growth factor binding protein-3 expression in intestinal epithelial cells.
J Pediatr Gastroenterol Nutr
; 42(2): 134-41, 2006 Feb.
Article
en En
| MEDLINE
| ID: mdl-16456404
ABSTRACT
OBJECTIVES:
Butyrate concentrations in the gastrointestinal tract vary greatly with age. In intestinal epithelial cells, butyrate enhances gene transcription by increasing histone acetylation, rendering the nucleosome open to transcription factors. However, it inhibits human insulin-like growth factor binding protein (hIGFBP)-3 expression. We therefore hypothesized that butyrate also acts by regulating transcription factor acetylation.METHODS:
Gene regulation was examined in Caco-2 cells. RNA stability was measured after interruption of transcription. The activity of deletion mutations of the hIGFBP-3 promoter was examined in reporter assays. Transcription factor binding to promoter DNA was analyzed.RESULTS:
Butyrate did not increase the transcription of a repressor because it inhibited hIGFBP-3 mRNA in the absence of protein synthesis. Nor did butyrate decrease the stability of hIGFBP-3 mRNA. Analysis of the hIGFBP-3 promoter demonstrated a butyrate-response element that included the binding sites for p300 and Sp1/Sp3. Transfection of Caco-2 cells with E1A, an inhibitor of p300 acetyltransferase activity, reversed the butyrate-induced repression of hIGFBP-3. Because Sp3 represses the initiation of transcription, we studied whether butyrate induced Sp3 acetylation. Electrophoretic mobility shift assays of nuclei extracted from Caco-2 cells treated with 5 mmol/L butyrate demonstrated an extra, heavier band in addition to the Sp3-DNA binding in untreated cells. This corresponded to a protein, detected only in butyrate treated cells, that was identified both by an anti-Sp3 antibody and by an anti-acetyl lysine antibody.CONCLUSIONS:
This study demonstrates that butyrate increases the acetylation of a nonhistone protein, Sp3, catalyzed by p300 acetyltransferase activity.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Acetilación
/
Factores de Transcripción
/
Butiratos
/
ARN
/
Regulación hacia Abajo
/
Proteínas de Ciclo Celular
/
Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina
/
Histona Acetiltransferasas
/
Factor de Transcripción Sp3
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Pediatr Gastroenterol Nutr
Año:
2006
Tipo del documento:
Article
País de afiliación:
Reino Unido