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Nat Commun. 2014 Jul 18;5:4450. doi: 10.1038/ncomms5450.

Loss of neuronal 3D chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction.

Author information

1
1] Instituto de Neurociencias (Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas), Avenida Santiago Ramón y Cajal s/n, Sant Joan d'Alacant, 03550 Alicante, Spain [2] [3].
2
1] Nencki Institute of Experimental Biology, Pasteura 3, 02-093 Warsaw, Poland [2].
3
Instituto de Neurociencias (Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas), Avenida Santiago Ramón y Cajal s/n, Sant Joan d'Alacant, 03550 Alicante, Spain.
4
Laboratory of Computational Biology, Estación Experimental de Aula Dei (Consejo Superior de Investigaciones Científicas) and Fundación ARAID, Avenida Montañana 1.005, 50059 Zaragoza, Spain.
5
Instituto de Investigación en Discapacidades Neurológicas (IDINE), Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Campus Biosanitario, C/Almansa, 14, Albacete 02006, Spain.
6
Nencki Institute of Experimental Biology, Pasteura 3, 02-093 Warsaw, Poland.

Abstract

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.

PMID:
25034090
DOI:
10.1038/ncomms5450
[Indexed for MEDLINE]

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