Wiedemann et al. have discovered two novel kinds of histones, the protein spools for DNA.

DNA strands usually coil around four histones—H2A, H2B, H3, and H4. But in certain situations, cells install alternatives. For example, CENP-A, a variant of H3, replaces conventional H3 at centromeres. Researchers haven't identified a new version of the H3 histone for 20 years, but Wiedemann et al. wondered if others remained to be discovered.

Searching the human genome for genes that resemble histone H3.1 revealed two close matches, which the researchers named H3.X and H3.Y. The genes occur in two other primates, the chimp and the rhesus macaque, but not in any other mammals with sequenced genomes or in other eukaryotes.

H3.X and H3.Y had previously been pegged as pseudogenes, but Wiedemann et al. showed that cells from several kinds of tumors—including bone, breast, and lung—make small amounts of RNA for one or both alternative histones. Healthy cells in the testis and much of the brain also tested positive for the variant histone RNA. The proteins might be useful in particular situations—cells could swap histones during stress, for example. When cells were crowded, the number of them expressing the variant histones shot up sixfold, the researchers found. Knockdown experiments suggested that H3.X and H3.Y promote cell growth.

The new histones remain mysterious in many ways. The researchers aren't sure why only primates appear to have them. And because only the H3.Y protein was detected in human cells, it's possible that the H3.X gene does not yield a protein and instead codes for a regulatory RNA.


et al
J. Cell Biol.