Quantitative and functional interrogation of parent-of-origin allelic expression biases in the brain
- Howard Hughes Medical Institute, Harvard University, United States
- Harvard University, United States
- University of Wyoming, United States
- Cell Press, United States
- National Chengchi University, Taiwan
Abstract
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.
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Ethics
Animal experimentation: This study was performed within the facilities of the Harvard University Faculty of Arts and Sciences (HU/FAS) in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animals were handled according to a protocol approved by the Harvard University Institutional Animal Care and Use Committee (IACUC; protocol #97-03). The HU/FAS animal care and use program maintains full AAALAC accreditation, is assured with OLAW (A3593-01), and is currently registered with the USDA. Every effort was made to minimize animal suffering during this study.
Reviewing Editor
- Sacha B Nelson, Brandeis University, United States
Version history
- Received: April 2, 2015
- Accepted: July 2, 2015
- Accepted Manuscript published: July 3, 2015 (version 1)
- Version of Record published: July 23, 2015 (version 2)
Copyright
© 2015, Perez et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Quantitative and functional interrogation of parent-of-origin allelic expression biases in the brain
eLife 4:e07860.
https://doi.org/10.7554/eLife.07860
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