ATX1-generated H3K4me3 is required for efficient elongation of transcription, not initiation, at ATX1-regulated genes.
ATX1-generated H3K4me3 is required for efficient elongation of transcription, not initiation, at ATX1-regulated genes.
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DOI：
10.1371/journal.pgen.1003111
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Avramova Z
中科院分区：
文献类型：
--
作者：
Ding Y;Ndamukong I;Xu Z;Lapko H;Fromm M;Avramova Z
三甲基化H3赖氨酸4（H3 K4 me 3）与转录活性基因相关，但其在转录过程中的功能尚不清楚。ATX 1（ARABIDOPSIS TRITHORAX 1）催化结构域的点突变，一种H3 K4甲基转移酶，和AtCOMPASS样亚基（与Set相关的拟南芥复合蛋白）的RNAi敲除被用来解决这个问题。我们证明，ATX 1和AtCOMPASS样的TBP（TATA结合蛋白）和Pol II在启动子的高水平积累所需的，这种要求是独立的催化组蛋白修饰活性。然而，催化功能是转录所必需的，因为H3 K4 me 3水平决定转录延伸的效率。H3 K4 me 3、ATX 1和AtCOMPASS样蛋白的作用可能与Trithorax激活的真核基因的转录有关。我们提供了一个明确的答案，关于组蛋白H3赖氨酸4三甲基化标记在两个ATX 1调节基因的转录中的作用的问题。尽管基因转录活性与核小体上H3 K4 me 3修饰水平之间的相关性已得到证实，但H3 K4 me 3是否有助于或仅仅是“注册”活性转录仍不清楚。另一个更广泛的相关性问题是组蛋白修饰蛋白是否需要招募的一般转录机制，从而发挥作用超出其催化活性。使用基因缺失和特定点突变分析的组合，我们解开重叠效应，并揭示H3 K4 me 3是不需要TBP/Pol II招聘启动子，但作为转录延伸的激活标记是至关重要的。迄今为止，关于H3 K4 me 3作为激活标记的作用的模糊性在很大程度上是由于ATX 1/AtCOMPASS功能的未知双重性：促进PIC组装和产生H3 K4 me 3作为转录延伸的激活标记。
Tri-methylated H3 lysine 4 (H3K4me3) is associated with transcriptionally active genes, but its function in the transcription process is still unclear. Point mutations in the catalytic domain of ATX1 (ARABIDOPSIS TRITHORAX1), a H3K4 methyltransferase, and RNAi knockdowns of subunits of the AtCOMPASS–like (Arabidopsis Complex Proteins Associated with Set) were used to address this question. We demonstrate that both ATX1 and AtCOMPASS–like are required for high level accumulation of TBP (TATA-binding protein) and Pol II at promoters and that this requirement is independent of the catalytic histone modifying activity. However, the catalytic function is critically required for transcription as H3K4me3 levels determine the efficiency of transcription elongation. The roles of H3K4me3, ATX1, and AtCOMPASS–like may be of a general relevance for transcription of Trithorax-activated eukaryotic genes. We provide a definitive answer to the question regarding the role of histone H3 lysine 4 tri-methylation marks in the transcription of two ATX1-regulated genes. Despite the proven correlation between the gene transcriptional activity and the level of H3K4me3 modification on the nucleosomes, whether H3K4me3 contributes to, or simply “registers,” active transcription has remained unclear. Another broader-relevance question is whether histone-modifying proteins are required for recruitment of the general transcription machinery, thus playing roles beyond their catalytic activity. Using a combination of gene deletion and specific point mutation analyses, we untangle overlapping effects and reveal that H3K4me3 is not required for TBP/Pol II recruitment to promoters but is critical as an activating mark for transcription elongation. The existing hitherto ambiguity about the role of H3K4me3 as an activating mark has been largely due to the unknown duality of the ATX1/AtCOMPASS functions: facilitating PIC assembly and producing H3K4me3 as an activating mark for transcription elongation.
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影响因子：
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