@article{StefanovicBarnettvanDuijvenbodenetal.2014,
  author    = {Stefanovic, Sonia and Barnett, Phil and van Duijvenboden, Karel and Weber, David and Gessler, Manfred and Christoffels, Vincent M.},
  title     = {GATA-dependent regulatory switches establish atrioventricular canal specificity during heart development},
  series = {Nature Communications},
  volume    = {5},
  journal   = {Nature Communications},
  number    = {3680},
  issn      = {2041-1723},
  doi       = {10.1038/ncomms4680},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121437},
  year      = {2014},
  abstract  = {The embryonic vertebrate heart tube develops an atrioventricular canal that divides the atrial and ventricular chambers, forms atrioventricular conduction tissue and organizes valve development. Here we assess the transcriptional mechanism underlying this localized differentiation process. We show that atrioventricular canal-specific enhancers are GATA-binding site-dependent and act as switches that repress gene activity in the chambers. We find that atrioventricular canal-specific gene loci are enriched in H3K27ac, a marker of active enhancers, in atrioventricular canal tissue and depleted in H3K27ac in chamber tissue. In the atrioventricular canal, Gata4 activates the enhancers in synergy with Bmp2/Smad signalling, leading to H3K27 acetylation. In contrast, in chambers, Gata4 cooperates with pan-cardiac Hdac1 and Hdac2 and chamber-specific Hey1 and Hey2, leading to H3K27 deacetylation and repression. We conclude that atrioventricular canal-specific enhancers are platforms integrating cardiac transcription factors, broadly active histone modification enzymes and localized co-factors to drive atrioventricular canal-specific gene activity.},
  language  = {en}
}
@article{LozovayaGataullinaTsintsadzeetal.2014,
  author    = {Lozovaya, N. and Gataullina, S. and Tsintsadze, T. and Tsintsadze, V. and Pallesi-Pocachard, E. and Minlebaev, M. and Goriounova, N. A. and Buhler, E. and Watrin, F. and Shityakov, S. and Becker, A. J. and Bordey, A. and Milh, M. and Scavarda, D. and Bulteau, C. and Dorfmuller, G. and Delalande, O. and Represa, A. and Cardoso, C. and Dulac, O. and Ben-Ari, Y. and Burnashev, N.},
  title     = {Selective suppression of excessive GluN2C expression rescues early epilepsy in a tuberous sclerosis murine model},
  series = {Nature Communications},
  volume    = {5},
  journal   = {Nature Communications},
  number    = {4563},
  doi       = {10.1038/ncomms5563},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121276},
  year      = {2014},
  abstract  = {Tuberous sclerosis complex (TSC), caused by dominant mutations in either TSC1 or TSC2 tumour suppressor genes is characterized by the presence of brain malformations, the cortical tubers that are thought to contribute to the generation of pharmacoresistant epilepsy. Here we report that tuberless heterozygote \(Tsc1^{+/-}\) mice show functional upregulation of cortical GluN2C-containing N-methyl-D-aspartate receptors (NMDARs) in an mTOR-dependent manner and exhibit recurrent, unprovoked seizures during early postnatal life (<P19). Seizures are generated intracortically in the granular layer of the neocortex. Slow kinetics of aberrant GluN2C-mediated currents in spiny stellate cells promotes excessive temporal integration of persistent NMDAR-mediated recurrent excitation and seizure generation. Accordingly, specific GluN2C/D antagonists block seizures in \(Tsc1^{+/-}\) mice in vivo and in vitro. Likewise, GluN2C expression is upregulated in TSC human surgical resections, and a GluN2C/D antagonist reduces paroxysmal hyperexcitability. Thus, GluN2C receptor constitutes a promising molecular target to treat epilepsy in TSC patients.},
  language  = {en}
}