Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 03760, Korea.
Ewha-JAX Cancer Immunotherapy Research Center, Ewha Womans University, Seoul 03760, Korea.
Nucleic Acids Res. 2020 Nov 4;48(19):10753-10767. doi: 10.1093/nar/gkaa781.
In yeast, NuA3 histone acetyltransferase (NuA3 HAT) promotes acetylation of histone H3 lysine 14 (H3K14) and transcription of a subset of genes through interaction between the Yng1 plant homeodomain (PHD) finger and H3K4me3. Although NuA3 HAT has multiple chromatin binding modules with distinct specificities, their interdependence and combinatorial actions in chromatin binding and transcription remain unknown. Modified peptide pulldown assays reveal that the Yng1 N-terminal region is important for the integrity of NuA3 HAT by mediating the interaction between core subunits and two methyl-binding proteins, Yng1 and Pdp3. We further uncover that NuA3 HAT contributes to the regulation of mRNA and lncRNA expression dynamics by antagonizing the histone deacetylases (HDACs) Rpd3S and Rpd3L. The Yng1 N-terminal region, the Nto1 PHD finger and Pdp3 are important for optimal induction of mRNA and lncRNA transcription repressed by the Set2-Rpd3S HDAC pathway, whereas the Yng1 PHD finger-H3K4me3 interaction affects transcriptional repression memory regulated by Rpd3L HDAC. These findings suggest that NuA3 HAT uses distinct chromatin readers to compete with two Rpd3-containing HDACs to optimize mRNA and lncRNA expression dynamics.
在酵母中，NuA3 组蛋白乙酰转移酶（NuA3 HAT）通过 Yng1 植物同源域（PHD）手指与 H3K4me3 之间的相互作用，促进组蛋白 H3 赖氨酸 14（H3K14）的乙酰化和一组基因的转录。尽管 NuA3 HAT 具有多个具有不同特异性的染色质结合模块，但它们在染色质结合和转录中的相互依赖性和组合作用仍然未知。修饰肽下拉测定揭示，Yng1 N 端区域通过介导核心亚基与两个甲基结合蛋白 Yng1 和 Pdp3 之间的相互作用，对 NuA3 HAT 的完整性很重要。我们进一步发现，NuA3 HAT 通过拮抗组蛋白去乙酰化酶（HDACs）Rpd3S 和 Rpd3L 来促进 mRNA 和 lncRNA 表达动力学的调节。Yng1 N 端区域、Nto1 PHD 手指和 Pdp3 对于由 Set2-Rpd3S HDAC 途径抑制的 mRNA 和 lncRNA 转录的最佳诱导很重要，而 Yng1 PHD 手指-H3K4me3 相互作用则影响由 Rpd3L HDAC 调节的转录抑制记忆。这些发现表明，NuA3 HAT 使用不同的染色质阅读器与两种包含 Rpd3 的 HDAC 竞争，以优化 mRNA 和 lncRNA 表达动力学。
