The Id (inhibitor of DNA binding or inhibitor of differentiation) helix–loop–helix proteins are involved in the regulation of cell growth, differentiation and cancer. The fact that the molecular mechanisms of liver regeneration are not completely understood prompted us to study the fate of Id2 in proliferating liver. Id2 increases in liver regeneration after partial hepatectomy, following the early induction of its gene. Co-immunoprecipitation shows that Id2 forms a complex with E2F4, p130 and mSin3A in quiescent liver and all these components are present at the c-myc promoter as shown using ChIP (chromatin immunoprecipitation). Activation of c-myc during hepatocyte priming (G0–G1 transition) correlates with the dissociation of Id2 and HDAC (histone deacetylase), albeit p130 remains bound at least until 6 h. Moreover, as the G0–G1 transition progresses, Id2 and HDAC again bind the c-myc promoter concomitantly with the repression of this gene. The time course of c-myc binding to the Id2 promoter, as determined by ChIP assays is compatible with a role of the oncoprotein as a transcriptional inducer of Id2 in liver regeneration. Immunohistochemical analysis shows that Id2 also increases in proliferating hepatocytes after bile duct ligation. In this case, the pattern of Id2 presence in the c-myc promoter parallels that found in regenerating liver. Our results may suggest a control role for Id2 in hepatocyte priming, through a p130 dissociation-independent regulation of c-myc.
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Research Article|
August 29 2006
Id2 leaves the chromatin of the E2F4–p130-controlled c-myc promoter during hepatocyte priming for liver regeneration
José L. Rodríguez;
José L. Rodríguez
1
*Departamento de Bioquímica y Biología Molecular, Universidad de València, València, Spain
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Juan Sandoval;
Juan Sandoval
1
*Departamento de Bioquímica y Biología Molecular, Universidad de València, València, Spain
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Gaetano Serviddio;
Gaetano Serviddio
2
†Departamento de Fisiología Universidad de València, València, Spain
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Juan Sastre;
Juan Sastre
†Departamento de Fisiología Universidad de València, València, Spain
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María Morante;
María Morante
*Departamento de Bioquímica y Biología Molecular, Universidad de València, València, Spain
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Maria-Giulia Perrelli;
Maria-Giulia Perrelli
‡Department of Clinical and Biological Sciences, University of Turin at San Luigi Gonzaga Hospital, Torino, Italy
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María L. Martínez-Chantar;
María L. Martínez-Chantar
§Metabolomics, CIC Biogune, Bizkaia, Spain
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José Viña;
José Viña
†Departamento de Fisiología Universidad de València, València, Spain
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Juan R. Viña;
Juan R. Viña
*Departamento de Bioquímica y Biología Molecular, Universidad de València, València, Spain
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José M. Mato;
José M. Mato
§Metabolomics, CIC Biogune, Bizkaia, Spain
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Matías A. Ávila;
Matías A. Ávila
∥División de Hepatología y Terapia Génica, CIMA, Departamento de Medicina Interna, Universidad de Navarra, Navarra, Spain
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Luis Franco;
Luis Franco
*Departamento de Bioquímica y Biología Molecular, Universidad de València, València, Spain
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Gerardo López-Rodas;
Gerardo López-Rodas
*Departamento de Bioquímica y Biología Molecular, Universidad de València, València, Spain
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Luis Torres
Luis Torres
3
*Departamento de Bioquímica y Biología Molecular, Universidad de València, València, Spain
3To whom correspondence should be addressed (email Luis.Torres@uv.es).
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Publisher: Portland Press Ltd
Received:
March 09 2006
Revision Received:
June 12 2006
Accepted:
June 16 2006
Accepted Manuscript online:
June 16 2006
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2006
Biochem J (2006) 398 (3): 431–437.
Article history
Received:
March 09 2006
Revision Received:
June 12 2006
Accepted:
June 16 2006
Accepted Manuscript online:
June 16 2006
Citation
José L. Rodríguez, Juan Sandoval, Gaetano Serviddio, Juan Sastre, María Morante, Maria-Giulia Perrelli, María L. Martínez-Chantar, José Viña, Juan R. Viña, José M. Mato, Matías A. Ávila, Luis Franco, Gerardo López-Rodas, Luis Torres; Id2 leaves the chromatin of the E2F4–p130-controlled c-myc promoter during hepatocyte priming for liver regeneration. Biochem J 15 September 2006; 398 (3): 431–437. doi: https://doi.org/10.1042/BJ20060380
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