The cell cycle requirement for silencing establishment.
Marc Meneghini, Hiten Madhani
Biochemistry and Biophysics, UCSF, 600 16th St, San Francisco, CA, 94143-2200, U.S.A.
For unknown reasons, the establishment of a silent heterochromatin domain in yeast requires passage through both S and M phase. We have shown that the histone variant H2A.Z functions in euchromatin to repel heterochromatin spread. Here we report that loss of silencing permits the deposition of H2A.Z and other euchromatic marks within the silenced region HMRa. We hypothesized that cell cycle requirements for silencing establishment reflects cell cycle-dependent removal of these euchromatin-promoting factors such as H2A.Z and methylated H3-K4 and K79. In agreement with our hypothesis, we found that depletion of H2A.Z, MeH3-K4, and MeH3-K79 within HMRa is associated with silencing establishment. A prediction of our model is that genetic removal of euchromatin-promoting factors should permit silencing establishment without passage through a cell cycle. We found that single deletions of the genes encoding H2A.Z (HTZ1), or the H3-K79 and H3-K4 methylases (DOT1 or SET1) cause partial bypass of the cell cycle requirements for silencing establishment. Double deletions displayed a synergistic effect. We identified Eos1 as an uncharacterized member of the Swi2 family of ATP-dependent chromatin remodeling enzymes that is a known target of the CDK Cdc28. We found that eos1Δ cells display delayed silencing establishment, suggesting that it is one of two or more partially redundant cell cycle-regulated factors involved in silencing establishment by acting to remove euchromatic marks.
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