Coordinated expression of replication-dependent histone genes from multiple loci promotes histone homeostasis in Drosophila
Coordinated expression of replication-dependent histone genes from multiple loci promotes histone homeostasis in Drosophila
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DOI：
10.1091/mbc.e22-11-0532
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发表时间：
2023-11-01
影响因子：
3.3
通讯作者：
Duronio, Robert J.
中科院分区：
文献类型：
--
作者：
Chaubal, Ashlesha;Waldern, Justin M.;Duronio, Robert J.
在S期产生大量的组蛋白对于正确的染色质形成和基因组完整性至关重要。这一过程部分是通过在后生动物基因组中的一个或多个簇中存在多个复制依赖（RD）组蛋白基因拷贝来实现的。此外，RD组蛋白基因簇与一个专门的核体，组蛋白基因座体（HLB），这有助于RD组蛋白mRNA的有效转录和3 '末端加工。这些簇中的所有五个RD组蛋白基因如何协调调节，使得产生的组蛋白既不太少也不太多，这一过程称为组蛋白稳态，尚未完全了解。本文探讨了黑腹果蝇和雄性果蝇中多个RD组蛋白基因座之间的协同调控机制。我们提供的证据，位于不同染色体位置的内源性和异位转基因组蛋白阵列在D。黑胃细胞，帮助维持适当的组蛋白mRNA水平。与该模型一致，在这两个物种中，我们发现单个组蛋白基因阵列可以独立地组装HLB，导致组蛋白转录活跃。我们的研究结果表明，HLB组装在协调RD组蛋白基因表达，以维持组蛋白稳态的作用。
Production of large amounts of histone proteins during S phase is critical for proper chromatin formation and genome integrity. This process is achieved in part by the presence of multiple copies of replication dependent (RD) histone genes that occur in one or more clusters in metazoan genomes. In addition, RD histone gene clusters are associated with a specialized nuclear body, the histone locus body (HLB), which facilitates efficient tran-scription and 3 ' end-processing of RD histone mRNA. How all five RD histone genes within these clusters are coordinately regulated such that neither too few nor too many histones are produced, a process referred to as histone homeostasis, is not fully understood. Here, we explored the mechanisms of coordinate regulation between multiple RD histone loci in Drosophila melanogaster and Drosophila virilis. We provide evidence for functional competition between endogenous and ectopic transgenic histone arrays located at different chromosomal locations in D. melanogaster that helps maintain proper histone mRNA levels. Consistent with this model, in both species we found that individual histone gene arrays can independently assemble an HLB that results in active histone transcription. Our findings suggest a role for HLB assembly in coordinating RD histone gene expression to maintain histone homeostasis.