Transcriptional activation triggers deposition and removal of the histone variant H3.3

Transcriptional activation triggers deposition and removal of the histone variant H3.3
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DOI:
10.1101/gad.1259805
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发表时间:
2005-04-01
影响因子:
10.5
通讯作者:
Ahmad, K
Ahmad, K
中科院分区:
生物学1区
文献类型:
--
作者:
Schwartz, BE;Ahmad, K

文献摘要

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真核细胞中的DNA被包装成核小体,核小体是染色质的结构单位。DNA和组蛋白都是非常长寿的,因为当染色质复制时,旧的DNA链和组蛋白会保留下来。相反,我们发现果蝇HSP 70基因在被诱导时迅速丢失组蛋白H3并获得变体H3.3组蛋白。组蛋白替换不发生在人工HSP 70启动子阵列,表明转录是必需的H3.3沉积。H3.3组蛋白在所有活性染色质和整个大的转录单位中富集,这意味着在转录延伸期间发生沉积。引人注目的是,我们观察到染色质结合的H3.3的稳定性在基因座之间不同:H3.3在持续活跃的rDNA基因处翻转,但在已关闭的诱导HSP 70基因处变得稳定。我们的结论是,H3.3沉积耦合到转录,并继续而基因是活跃的。重复的组蛋白替换提示了一种既能维持染色质结构又能在活性基因处接近DNA的机制。
DNA in eukaryotic cells is packaged into nucleosomes, the structural unit of chromatin. Both DNA and bulk histones are extremely long-lived, because old DNA strands and histones are retained when chromatin duplicates. In contrast, we find that the Drosophila HSP70 genes rapidly lose histone H3 and acquire variant H3.3 histones as they are induced. Histone replacement does not occur at artificial HSP70 promoter arrays, demonstrating that transcription is required for H3.3 deposition. The H3.3 histone is enriched in all active chromatin and throughout large transcription units, implying that deposition occurs during transcription elongation. Strikingly, we observed that the stability of chromatin-bound H3.3 differs between loci: H3.3 turns over at continually active rDNA genes, but becomes stable at induced HSP70 genes that have shut down. We conclude that H3.3 deposition is coupled to transcription, and continues while a gene is active. Repeated histone replacement suggests a mechanism to both maintain the structure of chromatin and access to DNA at active genes.