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Paternally biased X inactivation in mouse neonatal brain
Xu Wang1, Paul D Soloway, Andrew G Clark
1Deptartment of Molecular Biology and Genetics, Cornell University, 227 Biotechnology Building, Ithaca, NY 14853, USA.
Genome Biology
|July 29, 2010
Summary
Female mammals typically undergo random X inactivation. However, this study reveals a consistent paternal X chromosome under-expression bias in mouse tissues, suggesting an evolutionarily conserved epigenetic mechanism.
Area of Science:
- Epigenetics
- Genomics
- Mammalian Development
Background:
- X inactivation in female mammals was traditionally considered random.
- Recent advancements in allele-specific expression analysis enable quantitative reassessment.
Purpose of the Study:
- To quantitatively reassess the randomness of X inactivation.
- To investigate potential biases in X chromosome allele expression.
Main Methods:
- RNA-sequencing (RNA-seq) for initial observation of allele-specific expression.
- Pyrosequencing on mouse brain cDNA from reciprocal crosses.
- Analysis of allele-specific expression ratios controlling for Xce alleles.
Main Results:
- RNA-seq indicated a chromosome-wide bias towards paternal allele under-expression.
- Pyrosequencing confirmed a statistically significant tendency to under-express the paternal X chromosome in mouse brain.
- Quantified contributions of X inactivation sampling effects and cis-acting regulatory variation (eQTL).
Conclusions:
- Paternal X inactivation bias observed mirrors marsupials and eutherian extraembryonic tissues, suggesting conserved epigenetic regulation.
- Developed an efficient method to identify and confirm genes escaping X inactivation.
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01:58X-Inactivation
The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
01:58X-inactivation
The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...