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Sex Chromosome Biology in the Mammalian Kingdom
All biological differences between women and men originate from the sex chromosomes. Some 160
million years ago, the X and Y chromosomes were very similar, but since then the Y chromosome
has lost most of its genes, whereas the present X chromosome contains more than 1000 genes.
Hence, the dosage of X-encoded genes needs to be equalized between female (XX) and male (XY)
cells. This is achieved by random inactivation of one of the X chromosomes in female embryonic
cells. Consequently, women develop as a genetic mosaic for the maternal X (inherited from mother)
and the paternal X (inherited from father), with clinical implications related to X-linked diseases. In
the last few years, we have obtained evidence for a new molecular model to explain X chromosome
inactivation. This includes our discovery of a key role for the X-encoded protein RNF12, which counts
the number of X chromosomes per cell and initiates the random inactivation of one of them, if two X
chromosomes are counted. We aim to reveal many more of the intriguing molecular and cellular
aspects of X chromosome inactivation.