Unknown,Transcriptomics,Genomics,Proteomics

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

ABSTRACT: The interior of the eukaryotic cell nucleus is a highly organized 3D structure. In mature hippocampal and cortical pyramidal neurons, transcriptionally silent DNA is typically compacted in a few clusters referred to as chromocenters that are strongly stained with DNA intercalating agents like DAPI and whose function is still uncertain. We found that this 3D structure was severely disrupted by the incorporation of the chimeric histone H2BGFP into neuronal chromatin. Experiments in inducible and forebrain restricted bitransgenic mice demonstrated that the expression of this histone alters the higher-order organization of neuronal heterochromatin and causes a complex behavioral phenotype that includes hyperactivity, and social interaction, prepulse inhibition and cognitive defects. This phenotype was associated with highly specific transcriptional deficits that affected several serotonin receptor genes located at the edge of gene desert regions. Pharmacological and electrophysiological experiments indicate that this epigenetically-induced hyposerotonergic state may underlie the behavioral defects. Our results suggest a new role for perinuclear heterochromatin and chromocenter organization in the epigenetic regulation of neuronal gene expression and mental illness. We used microarrays to detect differential gene expression in transgenic mice expressing histone H2BGFP in the forebrain. We obtained triplicate samples (biological replicates) of either genotype (wild-type and H2BGFP mice). Each sample contained pooled total RNA from the hippocampi of 2 three-month old genotype-matched mice.

ORGANISM(S): Mus musculus

SUBMITTER: jose lopez

PROVIDER: E-GEOD-48437 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

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