Preferential occupancy of histone variant H2AZ at inactive promoters influences local histone modifications and chromatin remodeling
Preferential occupancy of histone variant H2AZ at inactive promoters influences local histone modifications and chromatin remodeling
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DOI：
10.1073/pnas.0507975102
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发表时间：
2005-12-20
影响因子：
11.1
通讯作者：
Workman, JL
中科院分区：
文献类型：
--
作者：
Li, B;Pattenden, SG;Workman, JL
酵母组蛋白变体H2 AZ（Htz 1）与转录激活、防止异染色质异位扩散和基因组完整性有关。我们的全基因组定位分析表明，Htz 1是广泛的，但非随机的，分布在整个基因组中的SWR 1依赖的方式。我们发现，与编码区相比，HTZ 1富集在基因间区域。其占有率与转录速率和RNA聚合酶11在不同生长条件下的富集成反比。然而，Htz 1似乎并不直接调节全基因组的转录抑制;相反，在失活条件下Htz 1的存在对于基因子集的最佳激活是必不可少的。此外，即使在那些启动子中，Htz 1高度富集，Htz 1通常也不负责核小体定位。最后，使用生物化学方法，我们证明了将Htz 1掺入核小体抑制了与转录相关的组蛋白修饰剂Dot 1，Set 2和NuA 4的活性，并减少了由染色质重塑复合物驱动的核小体动员。这些证据共同表明，Htz 1可能有助于标记静止的启动子进行适当的激活。
The yeast histone variant H2AZ (Htz1) is implicated in transcription activation, prevention of the ectopic spread of heterochromatin, and genome integrity. Our genome-wide localization analysis revealed that Htz1 is widely, but nonrandomly, distributed throughout the genome in an SWR1-dependent manner. We found that Htz1 is enriched in, intergenic regions compared with coding regions. Its occupancy is inversely proportional to transcription rates and the enrichment of the RNA polymerase 11 under different growth conditions. However, Htz1 does not seem to directly regulate transcription repression genome-wide; instead, the presence of Htz1 under the inactivated condition is essential for optimal activation of a subset of genes. In addition, Htz1 is not generally responsible for nucleosome positioning, even at those promoters where Htz1 is highly enriched. Finally, using a biochemical approach, we demonstrate that incorporation of Htz1 into nucleosomes inhibits activities of histone modifiers associated with transcription, Dot1, Set2, and NuA4 and reduces the nucleosome mobilization driven by chromatin remodeling complexes. These lines of evidence collectively suggest that Htz1 may serve to mark quiescent promoters for proper activation.