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Título : Loss of neuronal 3D chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction
Autor : Ito, Satomi; Magalska, Adriana; Alcaraz-Iborra, Manuel; López-Atalaya, Jose P.; Rovira, Víctor; Contreras-Moreira, Bruno ; Lipinski, Michal; Olivares, Román; Martínez-Hernández, José; Ruszczycki, Blazej; Luján, Rafael; Geijo-Barrientos, Emilio; Wilczynski, Grzegorz M.; Barco, Ángel
Fecha de publicación : jul-2014
Citación : Ito S, Magalska A, Alacaraz-Iborra M, López-Atalaya JP, Rovira V, Contreras-Moreira B, LIpinski M, Olivares R, Martínez-Hernández J, Ruszczycky B, Luján R, Geijo-Barrientos E, Wilczynsky GM, Barco A. Loss of neuronal 3D chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction. Nature Communications 5: art. n. 4450 (18 July 2014)
Resumen: The interior of the neuronal cell nucleus is a highly organized three-dimensional (3D) structure where regions of the genome that are linearly millions of bases apart establish sub-structures with specialized functions. To investigate neuronal chromatin organization and dynamics in vivo, we generated bitransgenic mice expressing GFP-tagged histone H2B in principal neurons of the forebrain. Surprisingly, the expression of this chimeric histone in mature neurons caused chromocenter declustering and disrupted the association of heterochromatin with the nuclear lamina. The loss of these structures did not affect neuronal viability but was associated with specific transcriptional and behavioural deficits related to serotonergic dysfunction. Overall, our results demonstrate that the 3D organization of chromatin within neuronal cells provides an additional level of epigenetic regulation of gene expression that critically impacts neuronal function. This in turn suggests that some loci associated with neuropsychiatric disorders may be particularly sensitive to changes in chromatin architecture.
Descripción : 48 Pags.- 7 Figs. The definitive version, with suppl. Figs. and Supp. Tabls., is available at: http://www.nature.com/ncomms/index.html
Versión del editor: http://dx.doi.org/10.1038/ncomms5450
URI : http://hdl.handle.net/10261/100969
DOI: 10.1038/ncomms5450
ISSN: 2041-1723
E-ISSN: 2041-1723
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