The loss of circadian PAR bZip transcription factors results in epilepsy.

Détails

Ressource 1Télécharger: BIB_2D08EE6EE491.P001.pdf (691.13 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_2D08EE6EE491
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The loss of circadian PAR bZip transcription factors results in epilepsy.
Périodique
Genes and Development
Auteur(s)
Gachon F., Fonjallaz P., Damiola F., Gos P., Kodama T., Zakany J., Duboule D., Petit B., Tafti M., Schibler U.
ISSN
0890-9369[print], 0890-9369[linking]
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
18
Numéro
12
Pages
1397-1412
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
DBP (albumin D-site-binding protein), HLF (hepatic leukemia factor), and TEF (thyrotroph embryonic factor) are the three members of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family. All three of these transcriptional regulatory proteins accumulate with robust circadian rhythms in tissues with high amplitudes of clock gene expression, such as the suprachiasmatic nucleus (SCN) and the liver. However, they are expressed at nearly invariable levels in most brain regions, in which clock gene expression only cycles with low amplitude. Here we show that mice deficient for all three PAR bZip proteins are highly susceptible to generalized spontaneous and audiogenic epilepsies that frequently are lethal. Transcriptome profiling revealed pyridoxal kinase (Pdxk) as a target gene of PAR bZip proteins in both liver and brain. Pyridoxal kinase converts vitamin B6 derivatives into pyridoxal phosphate (PLP), the coenzyme of many enzymes involved in amino acid and neurotransmitter metabolism. PAR bZip-deficient mice show decreased brain levels of PLP, serotonin, and dopamine, and such changes have previously been reported to cause epilepsies in other systems. Hence, the expression of some clock-controlled genes, such as Pdxk, may have to remain within narrow limits in the brain. This could explain why the circadian oscillator has evolved to generate only low-amplitude cycles in most brain regions.
Mots-clé
Animals, Basic-Leucine Zipper Transcription Factors, Brain/metabolism, Circadian Rhythm, DNA-Binding Proteins/deficiency, DNA-Binding Proteins/genetics, Electroencephalography, Electromyography, Epilepsy/etiology, Extracellular Matrix Proteins/analysis, Extracellular Matrix Proteins/deficiency, Glycoproteins/analysis, Glycoproteins/deficiency, Liver/metabolism, Mice, Mice, Knockout, Neurotransmitter Agents/metabolism, Pyridoxal Kinase/genetics, RNA, Messenger/analysis, Transcription Factors/deficiency, Transcription Factors/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 15:55
Dernière modification de la notice
20/08/2019 13:12
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