Histone trimethylation and the maintenance of transcriptional ON and OFF states by trxG and PcG proteins
Histone trimethylation and the maintenance of transcriptional ON and OFF states by trxG and PcG proteins
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DOI：
10.1101/gad.388706
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发表时间：
2006-08-01
影响因子：
10.5
通讯作者：
Mueller, Juerg
中科院分区：
文献类型：
--
作者：
Papp, Bernadett;Mueller, Juerg
Polycomb group （PcG）和trithorax group （trxG）蛋白作为拮抗调节因子，维持HOX和其他靶基因的转录OFF和ON状态。为了研究PcG/trxG控制的分子基础，我们分析了从发育中的果蝇纯化的Ubx（OFF）和Ubx（ON）细胞中HOX基因Ultrabithorax （Ubx）的染色质。我们发现PcG蛋白复合物PhoRC、PRC1和PRC2以及Trx蛋白都在OFF和ON状态下组成性地结合Polycomb response元件（PREs）。相比之下，trxG蛋白Ash1仅以ON状态结合；不是在pre，而是在转录起始位点的下游。在关闭状态下，我们发现整个Ubx基因在H3-K27、H3-K9和H4-K20位点存在广泛的三甲基化；即，整个上游控制，启动子和编码区域。在ON状态下，上游控制区在H3-K27、H3-K9和H4-K20位点也发生三甲基化，但在启动子和5 '编码区均不存在这三种修饰。我们对缺乏PcG组蛋白甲基转移酶（HMTase） E(z)或trxG HMTase Ash1的突变体的分析提供了强有力的证据，证明启动子和编码区组蛋白赖氨酸三甲基化的差异赋予了Ubx的转录ON和OFF状态。特别地，我们的研究结果表明，预系住的PcG蛋白复合物远距离作用产生PcG抑制的染色质，这些染色质在H3-K27、H3-K9和H4-K20位点被三甲基化，但trxG HMTase Ash1选择性地阻止启动子和编码区处于ON状态的三甲基化。
Polycomb group (PcG) and trithorax group (trxG) proteins act as antagonistic regulators to maintain transcriptional OFF and ON states of HOX and other target genes. To study the molecular basis of PcG/trxG control, we analyzed the chromatin of the HOX gene Ultrabithorax (Ubx) in Ubx(OFF) and Ubx(ON) cells purified from developing Drosophila. We find that PcG protein complexes PhoRC, PRC1, and PRC2 and the Trx protein are all constitutively bound to Polycomb response elements (PREs) in the OFF and ON state. In contrast, the trxG protein Ash1 is only bound in the ON state; not at PREs but downstream of the transcription start site. In the OFF state, we find extensive trimethylation at H3-K27, H3-K9, and H4-K20 across the entire Ubx gene; i.e., throughout the upstream control, promoter, and coding region. In the ON state, the upstream control region is also trimethylated at H3-K27, H3-K9, and H4-K20, but all three modifications are absent in the promoter and 5 ' coding region. Our analyses of mutants that lack the PcG histone methyltransferase (HMTase) E(z) or the trxG HMTase Ash1 provide strong evidence that differential histone lysine trimethylation at the promoter and in the coding region confers transcriptional ON and OFF states of Ubx. in particular, our results suggest that PRE-tethered PcG protein complexes act over long distances to generate Pc-repressed chromatin that is trimethylated at H3-K27, H3-K9, and H4-K20, but that the trxG HMTase Ash1 selectively prevents this trimethylation in the promoter and coding region in the ON state.