Meneghini Marc D, Wu Michelle, Madhani Hiten D
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.
Cell. 2003 Mar 7;112(5):725-36. doi: 10.1016/s0092-8674(03)00123-5.
Boundary elements hinder the spread of heterochromatin, yet these sites do not fully account for the preservation of adjacent euchromatin. Histone variant H2A.Z (Htz1 in yeast) replaces conventional H2A in many nucleosomes. Microarray analysis revealed that HTZ1-activated genes cluster near telomeres. The reduced expression of most of these genes in htz1Delta cells was reversed by the deletion of SIR2 (sir2Delta) suggesting that H2A.Z antagonizes telomeric silencing. Other Htz1-activated genes flank the silent HMR mating-type locus. Their requirement for Htz1 can be bypassed by sir2Delta or by a deletion encompassing the silencing nucleation sites in HMR. In htz1Delta cells, Sir2 and Sir3 spread into flanking euchromatic regions, producing changes in histone H4 acetylation and H3 4-methylation indicative of ectopic heterochromatin formation. Htz1 is enriched in these euchromatic regions and acts synergistically with a boundary element to prevent the spread of heterochromatin. Thus, euchromatin and heterochromatin each contains components that antagonize switching to the opposite chromatin state.
边界元件会阻碍异染色质的扩散，但这些位点并不能完全解释相邻常染色质得以保存的原因。组蛋白变体H2A.Z（酵母中的Htz1）在许多核小体中取代了传统的H2A。微阵列分析显示，HTZ1激活的基因聚集在端粒附近。在htz1Δ细胞中，大多数这些基因的表达降低，而通过缺失SIR2（sir2Δ）可使其逆转，这表明H2A.Z拮抗端粒沉默。其他Htz1激活的基因位于沉默的HMR交配型位点两侧。sir2Δ或缺失HMR中包含沉默成核位点的区域可绕过它们对Htz1的需求。在htz1Δ细胞中，Sir2和Sir3扩散到侧翼的常染色质区域，导致组蛋白H4乙酰化和H3 4-甲基化发生变化，这表明异位异染色质形成。Htz1在这些常染色质区域富集，并与边界元件协同作用以防止异染色质的扩散。因此，常染色质和异染色质各自都包含拮抗转换为相反染色质状态的成分。
