HDAC-3 participates in the repression of e2f-dependent gene transcription in primary differentiated neurons.
Activation of e2f-1 gene expression is an event that has been now established in many models of neuronal apoptosis. Accumulated E2F-1 protein has also been observed in post mortem brains obtained from patients suffering from different neurodegenerative diseases. We have previously shown in primary neuronal cultures that e2f-1 gene transcription was actively repressed in neuroprotective conditions through HDAC-dependent regulation on the E2F-responsive elements (E2F-REs) located in the e2f-1 gene promoter. Here, we further investigated the protein complex bound to these sites by gel shift analysis. We found that the specific protein binding to E2F-REs is altered in apoptotic conditions compared to neuroprotective conditions, suggesting that the proteic constituents of the complex are likely to be modified upon apoptosis onset. Indeed, Western blot analysis showed a time-dependent degradation of the Rb/E2F binding protein HDAC-3 during apoptosis, a degradation that is caspase-dependent. Altogether, these data point to HDAC-3 as a good candidate involved in the active e2f-1 repression necessary for neuroprotection.
Panteleeva
Irina
I
Laboratoire de Signalisation Moleculaire et Neurodegenerescence, EA#3433, Faculté de Médecine, 11 rue Humann, 67085 Strasbourg cedex, France.
Rouaux
Caroline
C
Larmet
Yves
Y
Boutillier
Stéphanie
S
Loeffler
Jean-Philippe
JP
Boutillier
Anne-Laurence
AL
D018797:Cell Cycle Proteins / Q000235:genetics*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D006655:Histone Deacetylases / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000502:physiology*; D000099186:Histone Deacetylase 3
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D006655:Histone Deacetylases; D014157:Transcription Factors; D000099186:Histone Deacetylase 3; C493753:E2F1 protein, human