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组蛋白基因替换揭示了H3K36在维持后生动物转录组保真度中的转录后作用。

Histone gene replacement reveals a post-transcriptional role for H3K36 in maintaining metazoan transcriptome fidelity.

作者信息

Meers Michael P, Henriques Telmo, Lavender Christopher A, McKay Daniel J, Strahl Brian D, Duronio Robert J, Adelman Karen, Matera A Gregory

机构信息

Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, United States.

Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, United States.

出版信息

Elife. 2017 Mar 27;6:e23249. doi: 10.7554/eLife.23249.

DOI:10.7554/eLife.23249
PMID:28346137
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5404926/
Abstract

Histone H3 lysine 36 methylation (H3K36me) is thought to participate in a host of co-transcriptional regulatory events. To study the function of this residue independent from the enzymes that modify it, we used a 'histone replacement' system in to generate a non-modifiable H3K36 lysine-to-arginine (H3K36R) mutant. We observed global dysregulation of mRNA levels in H3K36R animals that correlates with the incidence of H3K36me3. Similar to previous studies, we found that mutation of H3K36 also resulted in H4 hyperacetylation. However, neither cryptic transcription initiation, nor alternative pre-mRNA splicing, contributed to the observed changes in expression, in contrast with previously reported roles for H3K36me. Interestingly, knockdown of the RNA surveillance nuclease, Xrn1, and members of the CCR4-Not deadenylase complex, restored mRNA levels for a class of downregulated, H3K36me3-rich genes. We propose a post-transcriptional role for modification of replication-dependent H3K36 in the control of metazoan gene expression.

摘要

组蛋白H3赖氨酸36甲基化（H3K36me）被认为参与了许多共转录调控事件。为了独立于修饰该残基的酶来研究其功能，我们在[具体实验体系]中使用了一种“组蛋白置换”系统来生成不可修饰的H3K36赖氨酸到精氨酸（H3K36R）突变体。我们观察到H3K36R动物中mRNA水平的全局失调，这与H3K36me3的发生率相关。与先前的研究相似，我们发现H3K36的突变也导致了H4的高乙酰化。然而，与先前报道的H3K36me的作用相反，隐蔽转录起始和可变前体mRNA剪接均未导致观察到的表达变化。有趣的是，RNA监测核酸酶Xrn1以及CCR4-Not去腺苷酸化复合体成员的敲低恢复了一类下调的、富含H3K36me3的基因的mRNA水平。我们提出在控制后生动物基因表达中，复制依赖性H3K36的修饰具有转录后作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/16fb8cf4174f/elife-23249-resp-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/bc2175184401/elife-23249-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/500c34230a00/elife-23249-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/a728e1021eeb/elife-23249-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/7aa2e6a0393d/elife-23249-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/c59a4ead3c6b/elife-23249-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/09a1d3c5d6a1/elife-23249-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/3b55e4c86d2c/elife-23249-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/5a2e86a045df/elife-23249-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/233f9cc1e211/elife-23249-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/a285f3d6c661/elife-23249-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/be5869a301df/elife-23249-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/bef34e9736ab/elife-23249-resp-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/16fb8cf4174f/elife-23249-resp-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/bc2175184401/elife-23249-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/500c34230a00/elife-23249-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/a728e1021eeb/elife-23249-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/7aa2e6a0393d/elife-23249-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/c59a4ead3c6b/elife-23249-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/09a1d3c5d6a1/elife-23249-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/3b55e4c86d2c/elife-23249-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/5a2e86a045df/elife-23249-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/233f9cc1e211/elife-23249-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/a285f3d6c661/elife-23249-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/be5869a301df/elife-23249-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/bef34e9736ab/elife-23249-resp-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddc/5404926/16fb8cf4174f/elife-23249-resp-fig2.jpg

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