Direct regulation of nucleosome density by the conserved AAA-ATPase Yta7.

ABSTRACT

Yta7 is a highly conserved bromodomain-containing protein with AAA-ATPase homology originally implicated in heterochromatin boundary function in Saccharomyces cerevisiae. Although increased activity of the human ortholog has been implicated in malignant breast tumors, Yta7's precise mode of action is unknown. Transcriptional analysis in yeast cells revealed a role for Yta7 and its ATPase function in gene induction, including galactose- and sporulation-induced transcription. This requirement was direct and activating, because Yta7 associated with the GAL gene cluster only upon transcriptional induction. Suggestive of a role in transcriptional elongation, Yta7 localized to the ORFs of highly transcribed genes. Intriguingly, the yta7Δ mutant's transcriptional defects were partially suppressed by decreased dosage of histones H3 and H4. Consistent with this suppression, cells lacking Yta7 exhibited both increased levels of chromatin-incorporated histone H3 and decreased nucleosome spacing. Importantly, this modulation of H3 levels occurred independently of changes in H3 transcript level. Because Yta7 binds histone H3 in vitro, these results suggested a direct role for Yta7 in H3 eviction or degradation. Further, local loss of Yta7 activity at a long inducible gene resulted in accumulation of H3 at the 3' end upon transcriptional activation, implying Yta7 may regulate H3 cotranscriptionally.