Parental biases influence brain
The body's tendency to silence the expression of one parental allele in favor of the other -- a practice known as genomic imprinting -- is much more widespread than scientists have believed, according to a new genome-wide study in mice, published online this week in linkurl:Science.;http://www.sciencemag.org/
The study found that the number of genes in mouse brains with a bias toward either the maternal or paternal allele is thirteen times higher than previously thought. Kessa LigerroWikimedia
The body's tendency to silence the expression of one parental allele in favor of the other -- a practice known as genomic imprinting -- is much more widespread than scientists have believed, according to a new genome-wide study in mice, published online this week in linkurl:Science.
The study found that the number of genes in mouse brains with a bias toward either the maternal or paternal allele is thirteen times higher than previously thought.
"Overall, the results tell us that imprinting is a major mode of epigenetic regulation," said study author linkurl:Catherine Dulac;http://golgi.harvard.edu/faculty/faculty_profile.php?f=catherine-dulac at Harvard University. In addition, she and her colleagues argue that understanding imprinting in the brain may shed light on sex-specific brain diseases.
Genomic imprinting is a type of epigenetic regulation, in which chemical reactions cause changes in gene expression without altering the underlying DNA. Over the last ten years, many researchers have tried brute-force methods like microarrays to determine the number of imprinted genes, said linkurl:Michael O'Neill,;http://www.mcb.uconn.edu/fac.php?name=oneillmj a molecular biologist at the University of Connecticut who was not involved in the research. "This is the best, most comprehensive study I've seen thus far," he said. "They can see very subtle parental biases, which you can't typically see with other methods."
Prior to this study, only around 100 imprinted genes had been identified -- most either stumbled over or found on a case-by-case basis. Of those 100 genes, the majority are involved in embryonic development, but the second most frequent phenotype is brain function.
Dulac and her colleagues decided to take a closer look at the role of imprinted genes in the brain by deep sequencing the RNA from the brains of mice using a high-resolution sequencing technology and comparing the expression patterns to the RNA of the parental mice. By doing so, they identified over 1,300 protein-coding genes where a maternal or paternal allele is preferentially expressed. "One hundred genes is a pretty marginal phenomenon," said Dulac. "But 1,300! That's a lot."
And that was just the beginning of the surprises, Dulac told The Scientist.
In addition to the sheer quantity of imprinted genes they identified, the team was surprised to find that genomic imprinting commonly varies among brain regions and between sexes. For example, in a region of the hypothalamus involved in the control of maternal and mating behavior, females had three times more imprinted genes than males. They also found that Interleukin 18,
a gene linked with sex-specific diseases in the brain, is subject to complex parental imprinting effects.
Finally, while analyzing both embryonic and adult mouse brains, they found that there is a preferential expression of maternal genes in the developing brain and the opposite -- a major paternal contribution -- in the adult brain. That implies that genomic imprinting is a dynamic process, which can change at some point during development. The results confirm a linkurl:1996 study;http://www.ncbi.nlm.nih.gov/pubmed/8861727 of chimeric mice that suggested maternal genes are especially important for brain development, said Dulac.
DNA methylation is the best-recognized method of genomic imprinting, but it is likely not the only one, O'Neill added. "I would guess, that with so many imprinted genes showing subtle and dynamic parent-of-origin effects, we're seeing a different type of imprinting may not involve differential methylation," said O'Neill. "We may be seeing a cohort of genes with a completely different imprinting mechanism. That's really cool too."
C. Gregg et al. "High Resolution Analysis of Parent-of-Origin Allelic Expression in the Mouse Brain," Science, published online July 8, 2010, doi:10.1126/science.1190830.
C. Gregg et al. "Sex-Specific Parent-of-Origin Allelic Expression in the Mouse Brain," Science, published online July 8, 2010, doi:10.1126/science.1190831.
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[13th September 2002]*linkurl:Cancer epigenetics enters the mainstream;http://www.the-scientist.com/article/display/15539/
[20th June 2005]