NGF-dependent and tissue-specific transcription of vgf is regulated by a CREB-p300 and bHLH factor interaction.
Neurotrophins support neuronal survival, development, and plasticity through processes requiring gene expression. We studied how vgf target gene transcription is mediated by a critical promoter region containing E-box, CCAAT and cAMP response element (CRE) sites. The p300 acetylase was present in two distinct protein complexes bound to this region. One complex, containing HEB (ubiquitous basic helix-loop-helix (bHLH)), bound the promoter in non-neuronal cells and was involved in repressing vgf expression. Neurotrophin-dependent transcription was mediated by the second complex, specific for neuronal cells, which included CRE binding protein and MASH1 (neuro-specific bHLH), bound the CCAAT motif, and was target of neurotrophin signalling. The interaction, mediated by p300, of different transcription factors may add specificity to the neurotrophin response.
Mandolesi
Georgia
G
Centro Acidi Nucleici CNR, Dipartimento Genetica e Biologia Molecolare, Università La Sapienza, P. le A. Moro 5, 00185 Rome, Italy.
Gargano
Silvia
S
Pennuto
Maria
M
Illi
Barbara
B
Molfetta
Rosa
R
Soucek
Laura
L
Mosca
Laura
L
Levi
Andrea
A
Jucker
Richard
R
Nasi
Sergio
S
D016475:3T3 Cells; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D050881:E1A-Associated p300 Protein; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D009414:Nerve Growth Factors; D009479:Neuropeptides; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D016716:PC12 Cells; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D051381:Rats; D015534:Trans-Activators / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D050881:E1A-Associated p300 Protein; D020932:Nerve Growth Factor; D009414:Nerve Growth Factors; D009479:Neuropeptides; D009687:Nuclear Proteins; D011506:Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C499318:Ascl1 protein, rat; C489532:Tcf12 protein, mouse; C512697:Vgf protein, mouse; C062040:Vgf protein, rat; C073366:TCF12 protein, human; C494361:Ep300 protein, mouse; C494362:Ep300 protein, rat