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Twine, Janitz, Wilkins, Janitz (2013) Sequencing of hippocampal and cerebellar transcriptomes provides new insights into the complexity of gene regulation in the human brain Neuroscience letters 541() 263-8


The hippocampus and cerebellum represent anatomically and functionally distinct parts of the human brain. The RNA-Seq technique makes it possible to investigate the human transcriptome with unprecedented resolution, allowing identification of differential mRNA splicing and promoter usage on a genome-wide scale. We undertook whole-mRNA sequencing of samples from the human hippocampus and cerebellum. A bioinformatic analysis revealed distinct expression patterns of genes related to the molecular physiology of neurons and glial cells. Upregulated genes in hippocampal tissue included serpin peptidase inhibitor, clade A (SERPINA3), lymphocyte antigen 6 complex, locus H (LY6H) and transthyretin (TTR). In cerebellum, the cerebellin 3 precursor (CLBN3) and Zic family member 4 (ZIC4) genes were significantly upregulated. These changes were validated in independent donor samples by qRT-PCR. The hippocampus and the cerebellum showed striking differences in splicing patterns and promoter usage. A notable example of this was the gene for NGFI-A binding protein 2 (NAB2), which displayed tissue-specific isoforms which may affect its function as a transcriptional repressor.


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