Howard Hughes Medical Institute, Department of Genetics ; Harvard Medical School
The phenomena of X-chromosome inactivation (XCI) and autosomal imprinting both violate the dogma of genetic equality in that maternally and paternally inherited information are not expressed equivalently. In XCI, one of the two female X chromosomes is silenced for dosage compensation of XX and XY individuals. In autosomal imprinting, parental marks determine which of two autosomal alleles will be expressed in the embryo. Although XCI and autosomal imprinting initially appeared distinct, molecular evidence now reveals many similarities. Among them are cis-acting control centers, long-distance regulation, differential DNA methylation, differential use of chromatin markings, and the presence of noncoding and antisense RNAs. Does XCI and genomic imprinting have a common evolutionary origin? Indeed, the earliest form of XCI is imprinted and occurs only on the paternal X. This is still the case in marsupials of today and in the extraembryonic tissues of some eutherians such as cows and rodents. I will present our latest work towards understanding the origin of imprinted XCI in the mouse and then debate whether this sheds light on the ancestral mechanism of imprinting.
Sleutals, F. and Barlow, D. 2002. The origins of genomic imprinting in mammals. In Homology Effects, ed. Dunlap and Wu. pp. 119-154.
Lee, J.T. 2003. Molecular links between X-inactivation and autosomal imprinting: X-inactivation as a driving force for the evolution of imprinting. Curr Biol 13, R242-R254.
Huynh, K. D. and Lee, J.T. 2003. Inheritance of a pre-inactivated paternal X chromosome in early mouse embryos. Nature 426, 857-862.
Okamoto et al. 2004. Epigenetic dynamics of imprinted X-inactivation during early mouse development. Science 303, 644-649.
Huynh, K. D. and Lee, J.T. 2005. X-chromosome inactivation: a hypothesis linking ontogeny and phylogeny. Nat Rev Genet. 6, 410-418.
Reik, W. and Lewis, A. 2005. Co-evolution of X-chromosome inactivation and imprinting in mammals. Nat Rev Genet. 6, 403-410.