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Fifty years ago, Mary Lyon hypothesised that one of the two X chromosomes in female mammalian cells is inactivated at random during early embryogenesis and that the inactive X is then stably maintained through all subsequent cell divisions. Although Lyon's hypothesis is now widely regarded as fact, we should not forget that her conceptual leap met with considerable resistance from the scientific establishment at the time - a common response to new ideas. Taking this point as a theme, I discuss our current understanding of the molecular mechanism of chromosome silencing in X-chromosome inactivation and focus on topics where new findings are challenging the prevailing view.

Original publication




Journal article



Publication Date





5057 - 5065


Animals, Humans, Mice, Models, Biological, Polycomb-Group Proteins, Protein Structure, Tertiary, RNA, RNA, Long Noncoding, RNA, Untranslated, Repressor Proteins, X Chromosome Inactivation