Transcription of a 5' extended mRNA isoform directs dynamic chromatin changes and interference of a downstream promoter.
Transcription of a 5' extended mRNA isoform directs dynamic chromatin changes and interference of a downstream promoter.
复制标题
DOI：
10.7554/elife.27420
复制
发表时间：
2017-09-14
期刊：
影响因子：
7.7
通讯作者：
van Werven FJ
中科院分区：
文献类型：
--
作者：
Chia M;Tresenrider A;Chen J;Spedale G;Jorgensen V;Ünal E;van Werven FJ
细胞分化程序需要基因表达的动态调控。在酿酒酵母减数分裂前期，着丝粒复合体Ndc80的表达被一个5 '长的未解码Ndc80转录异构体下调。在这里，我们证明了一种转录干扰机制，负责抑制编码NDC80 mRNA亚型的表达。来自远端NDC80启动子的转录指导set1依赖的组蛋白H3K4二甲基化和set2依赖的H3K36三甲基化，从而在下游规范NDC80启动子中建立抑制染色质状态。因此，在减数分裂前期NDC80的表达受到抑制。这里描述的转录机制是快速可逆的，适应微调基因表达，并依赖于Set2和Set3组蛋白去乙酰化酶复合物。因此，5 '延伸的mRNA异构体的表达在下游启动子处引起转录干扰。我们证明这是促进细胞分化过程中基因表达动态变化的有效机制。
Cell differentiation programs require dynamic regulation of gene expression. During meiotic prophase in Saccharomyces cerevisiae, expression of the kinetochore complex subunit Ndc80 is downregulated by a 5’ extended long undecoded NDC80 transcript isoform. Here we demonstrate a transcriptional interference mechanism that is responsible for inhibiting expression of the coding NDC80 mRNA isoform. Transcription from a distal NDC80 promoter directs Set1-dependent histone H3K4 dimethylation and Set2-dependent H3K36 trimethylation to establish a repressive chromatin state in the downstream canonical NDC80 promoter. As a consequence, NDC80 expression is repressed during meiotic prophase. The transcriptional mechanism described here is rapidly reversible, adaptable to fine-tune gene expression, and relies on Set2 and the Set3 histone deacetylase complex. Thus, expression of a 5’ extended mRNA isoform causes transcriptional interference at the downstream promoter. We demonstrate that this is an effective mechanism to promote dynamic changes in gene expression during cell differentiation.