1. Neuroscience
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Quantitative and functional interrogation of parent-of-origin allelic expression biases in the brain

  1. Julio D Perez
  2. Nimrod D Rubinstein
  3. Daniel E Fernandez
  4. Stephen W Santoro
  5. Leigh A Needleman
  6. Olivia Ho-Shing
  7. John J Choi
  8. Mariela Zirlinger
  9. Shau-Kwaun Chen
  10. Jun S Liu
  11. Catherine Dulac  Is a corresponding author
  1. Howard Hughes Medical Institute, Harvard University, United States
  2. Harvard University, United States
  3. University of Wyoming, United States
  4. Cell Press, United States
  5. National Chengchi University, Taiwan
Research Article
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Cite this article as: eLife 2015;4:e07860 doi: 10.7554/eLife.07860

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.

Article and author information

Author details

  1. Julio D Perez

    Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  2. Nimrod D Rubinstein

    Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  3. Daniel E Fernandez

    Department of Statistics, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  4. Stephen W Santoro

    Neuroscience Program, Department of Zoology and Physiology, University of Wyoming, Laramie, United States
    Competing interests
    No competing interests declared.
  5. Leigh A Needleman

    Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  6. Olivia Ho-Shing

    Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  7. John J Choi

    Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  8. Mariela Zirlinger

    Cell Press, Cambridge, United States
    Competing interests
    No competing interests declared.
  9. Shau-Kwaun Chen

    National Chengchi University, Tapei, Taiwan
    Competing interests
    No competing interests declared.
  10. Jun S Liu

    Department of Statistics, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  11. Catherine Dulac

    Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, United States
    For correspondence
    dulac@fas.harvard.edu
    Competing interests
    Catherine Dulac, Senior editor, eLife.

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

  1. Sacha B Nelson, Brandeis University, United States

Publication history

  1. Received: April 2, 2015
  2. Accepted: July 2, 2015
  3. Accepted Manuscript published: July 3, 2015 (version 1)
  4. 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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