Distinct roles of Polycomb group gene products in transcriptionally repressed and active domains of Hoxb8
Distinct roles of Polycomb group gene products in transcriptionally repressed and active domains of Hoxb8
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DOI：
10.1242/dev.02405
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发表时间：
2006-06-15
期刊：
影响因子：
4.6
通讯作者：
Koseki, Haruhiko
中科院分区：
文献类型：
--
作者：
Fujimura, Yu-ichi;Isono, Kyo-ichi;Koseki, Haruhiko
为了解决 Polycomb 基团 (PcG) 介导的 Hox 基因表达抑制的分子机制，我们重点研究了表达和非表达组织中 PcG 基因产物与 Hoxb8 基因侧翼区域的结合模式。同时，我们跟踪了赖氨酸 9 上乙酰化的转录活性 H3 (H3-K9) 和赖氨酸 4 上的甲基化 (H3-K4) 以及赖氨酸 27 上的转录失活染色质三甲基化 (H3-K27) 的转录活性 H3 的组蛋白标记的分布。染色质免疫沉淀显示，PcG 蛋白与 Hoxb8 周围的 H3-K9 乙酰化和 H3-K27 三甲基化的关联在表达和不表达该基因的组织中是不同的。我们发现这些表观遗传标记的发育变化在时间上与 PcG 突变体中 Hox 基因的错误表达一致。使用损害 PcG 2 类成分 Rnf2 的突变等位基因或减少 H3-K27 三甲基化的 Suz12 突变进行功能分析，揭示由三甲基化 H3-K27 介导的 1 类和 2 类 PcG 复合物之间的相互作用，在维持其表达域外的 Hox 基因抑制中发挥决定性作用。在表达域内，2 类 PcG 复合物似乎通过 H3-K9 乙酰化的深度调节来维持转录活性状态。本研究表明 2 类 PcG 复合物在 Hoxb8 基因的转录抑制域和活性域中具有不同的作用。
To address the molecular mechanisms underlying Polycomb group (PcG)-mediated repression of Hox gene expression, we havefocused on the binding patterns of PcG gene products to the flanking regions of the Hoxb8 gene in expressing and non-expressing tissues. In parallel, we followed the distribution of histone marks of transcriptionally active H3 acetylated on lysine 9 (H3-K9) and methylated on lysine 4 (H3-K4), and of transcriptionally inactive chromatin trimethylated on lysine 27 (H3-K27). Chromatin immunoprecipitation revealed that the association of PcG proteins, and H3-K9 acetylation and H3-K27 trimethylation around Hoxb8 were distinct in tissues expressing and not expressing the gene. We show that developmental changes of these epigenetic marks temporally coincide with the misexpression of Hox genes in PcG mutants. Functional analyses, using mutant alleles impairing the PcG class 2 component Rnf2 or the Suz12 mutation decreasing H3-K27 trimethylation, revealed that interactions between class 1 and class 2 PcG complexes, mediated by trimethylated H3-K27, play decisive roles in the maintenance of Hox gene repression outside their expression domain. Within the expression domains, class 2 PcG complexes appeared to maintain the transcriptionally active status via profound regulation of H3-K9 acetylation. The present study indicates distinct roles for class 2 PcG complexes in transcriptionally repressed and active domains of Hoxb8 gene.