Id2 leaves the chromatin of the E2F4-p130-controlled c-myc promoter during hepatocyte priming for liver regeneration.
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.
Rodríguez
José L
JL
Departamento de Bioquímica y Biología Molecular, Universidad de València, València, Spain.
Sandoval
Juan
J
Serviddio
Gaetano
G
Sastre
Juan
J
Morante
María
M
Perrelli
Maria-Giulia
MG
Martínez-Chantar
María L
ML
Viña
José
J
Viña
Juan R
JR
Mato
José M
JM
Avila
Matías A
MA
Franco
Luis
L
López-Rodas
Gerardo
G
Torres
Luis
L
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D050704:E2F4 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D011401:Promoter Regions, Genetic / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D015854:Up-Regulation
D002352:Carrier Proteins; D002843:Chromatin; D050704:E2F4 Transcription Factor; C497451:Id2 protein, rat; D051797:Inhibitor of Differentiation Protein 2; C430714:Plcl1 protein, rat; D016271:Proto-Oncogene Proteins c-myc