Person:

Perez, Julio

The maternal and paternal genomes play different roles in mammalian brains as a result of genomic imprinting, an epigenetic regulation leading to differential expression of the parental alleles of some genes. Here we investigate genomic imprinting in the cerebellum using a newly developed Bayesian statistical model that provides unprecedented transcript-level resolution. We uncover 160 imprinted transcripts, including 41 novel and independently validated imprinted genes. Strikingly, many genes exhibit parentally biased—rather than monoallelic—expression, with different magnitudes according to age, organ, and brain region. Developmental changes in parental bias and overall gene expression are strongly correlated, suggesting combined roles in regulating gene dosage. Finally, brain-specific deletion of the paternal, but not maternal, allele of the paternally-biased Bcl-x, (Bcl2l1) results in loss of specific neuron types, supporting the functional significance of parental biases. These findings reveal the remarkable complexity of genomic imprinting, with important implications for understanding the normal and diseased brain. DOI: http://dx.doi.org/10.7554/eLife.07860.001

Most mammalian genes are equally expressed from the two inherited parental alleles. However, a puzzling subgroup known as imprinted genes are preferentially expressed from either the maternally- or paternally-inherited copy. Interestingly, many imprinted genes identified so far are expressed in the brain and mutations cause striking defects in brain development and function, in some cases leading to mental disorders such as autism-spectrum disorders. To better understand the extent of genomic imprinting in the brain and gain insights into its potential roles, I have investigated genomic imprinting in the Cerebellum. The Cerebellum provides several experimental advantages and has interesting functions, some of them recently associated with autism. Using RNA-Seq I have profiled the maternal and paternal transcriptomes in the developing and adult mouse Cerebellum, and uncovered 124 genes under imprinting regulation, 40 of which had not been described as imprinted before. Interestingly, the parental bias of 50% of detected genes are regulated according to age. Furthermore, parental biases appear to substantially vary across adult brain regions and are often not observed in non-brain tissues. Finally, I observed an overrepresentation of genes involved in programed cell death among imprinted genes, suggesting that the phenomenon of imprinting may target this pathway with interesting functional implications.