When H2A.Z is added in vitro to replace H2A, the resulting nucleosomes are resistant to higher order condensation. But the in vivo significance of this result was unclear. Now, along comes the new array data. “We got this bizarre result,” says Madhani. “The genes that were repressed [after Htz1 loss] were clustered near telomeres.” Other repressed genes were huddled near the mating region, which is the other major silenced region in yeast chromatin.
The repression was partially reversed by deleting either the silencing protein Sir2 or a mating region silencing element. Repression after Htz1 deletion was associated with the spread of Sir2 and Sir3 from both telomeres and the mating region into normally active, euchromatic regions, and reduced levels of euchromatin-associated marks such as acetylated histone H4.
A simple spreading event may not explain all, however. Only 30% of genes near telomeres require Htz1 to maintain their expression levels. And although Sir2 and acetylated H4 levels changed in euchromatic regions when Htz1 was deleted, they never reached the levels seen in heterochromatin.
Loss of a chromatin boundary element showed synergistic effects with Htz1 deletion, and Madhani believes there may be still other systems that protect against the insidious spread of heterochromatin. When those systems are understood, he says, we may realize that euchromatin has its own maintenance and spreading mechanisms and thus is “morally equivalent to heterochromatin.” ▪