Developmental timing in Dictyostelium is regulated by the Set1 histone methyltransferase
Developmental timing in Dictyostelium is regulated by the Set1 histone methyltransferase
复制标题
DOI：
10.1016/j.ydbio.2005.12.054
复制
发表时间：
2006-04-15
影响因子：
2.7
通讯作者：
Singer, RH
中科院分区：
文献类型：
--
作者：
Chubb, JR;Bloomfield, G;Singer, RH
组蛋白修饰酶具有巨大的潜力，可以调节分化过程中基因表达的大规模变化。目前尚不清楚历史修改的不同组合如何在发育过程中协调转录制度。我们发现，历史上的H3(H3K4)赖氨酸4的不同甲基化状态标志着简单真核生物Dictyostelials的不同发育阶段。我们证明了负责H3K4的所有单甲基化、双甲基化和三甲基化的酶是组蛋白甲基转移酶Set1的Dictyostoma同源物。在没有Sell的情况下，细胞表现出异常快速的发育，其特征是阿米巴虫早熟聚集成多细胞聚集体。早期分化标志物在生长中的set1细胞中大量表达，表明分化程序在生长过程中被异位激活。这种表型是由Set1催化活性的丧失引起的。SET1突变体诱导野生型细胞提前分化，表明Set1调节一种细胞外因子的产生，这是正确感知生长条件所必需的。对set1突变体的微阵列分析显示，错误表达的基因在基因组上聚集在一起，这表明在基因簇中对染色质介导的事件的调节需要Sell。(C)2006 Elsevier Inc.保留所有权利。
Histone-modifying enzymes have enormous potential as regulators of the large-scale changes in gene expression occurring during differentiation. It is unclear how different combinations of historic modification coordinate regimes of transcription during development. We show that different methylation states of lysine 4 of historic H3 (H3K4) mark distinct developmental phases of the simple eukaryote, Dictyostelium. We demonstrate that the enzyme responsible for all mono, di and tri-methylation of H3K4 is the Dictyostelium homolog of the Set1 histone methyltransferase. In the absence of sell, cells display unusually rapid development,, characterized by precocious aggregation of amoebae into multicellular aggregates. Early differentiation markers are abundantly expressed in growing set1 cells, indicating the differentiation program is ectopically activated during growth. This phenotype is caused specifically by the loss of Set1 catalytic activity. Set1 mutants induce premature differentiation in wild-type cells, indicating Set1 regulates production of an extra-cellular factor required for the correct perception of growth conditions. Microarray analysis of the set1 mutants reveals genomic clustering of mis-expressed genes, suggesting a requirement for sell in the regulation of chromatin-mediated events at gene clusters. (c) 2006 Elsevier Inc All rights reserved.