Hardy Sara, Jacques Pierre-Etienne, Gévry Nicolas, Forest Audrey, Fortin Marie-Eve, Laflamme Liette, Gaudreau Luc, Robert François
Institut de recherches cliniques de Montréal, Montréal, Québec, Canada.
PLoS Genet. 2009 Oct;5(10):e1000687. doi: 10.1371/journal.pgen.1000687. Epub 2009 Oct 16.
A role for variant histone H2A.Z in gene expression is now well established but little is known about the mechanisms by which it operates. Using a combination of ChIP-chip, knockdown and expression profiling experiments, we show that upon gene induction, human H2A.Z associates with gene promoters and helps in recruiting the transcriptional machinery. Surprisingly, we also found that H2A.Z is randomly incorporated in the genome at low levels and that active transcription antagonizes this incorporation in transcribed regions. After cessation of transcription, random H2A.Z quickly reappears on genes, demonstrating that this incorporation utilizes an active mechanism. Within facultative heterochromatin, we observe a hyper accumulation of the variant histone, which might be due to the lack of transcription in these regions. These results show how chromatin structure and transcription can antagonize each other, therefore shaping chromatin and controlling gene expression.
现在已经充分证实了变体组蛋白H2A.Z在基因表达中的作用，但对其发挥作用的机制却知之甚少。通过结合染色质免疫沉淀芯片（ChIP-chip）、基因敲低和表达谱分析实验，我们发现，在基因诱导时，人类H2A.Z与基因启动子结合，并有助于募集转录机制。令人惊讶的是，我们还发现H2A.Z以低水平随机整合到基因组中，而活跃转录会拮抗其在转录区域的整合。转录停止后，随机整合的H2A.Z会迅速重新出现在基因上，这表明这种整合利用了一种活跃机制。在兼性异染色质中，我们观察到该变体组蛋白的高度积累，这可能是由于这些区域缺乏转录所致。这些结果表明染色质结构和转录如何相互拮抗，从而塑造染色质并控制基因表达。
