A motif within SET-domain proteins binds single-stranded nucleic acids and transcribed and supercoiled DNAs and can interfere with assembly of nucleosomes
A motif within SET-domain proteins binds single-stranded nucleic acids and transcribed and supercoiled DNAs and can interfere with assembly of nucleosomes
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DOI：
10.1128/mcb.25.5.1891-1899.2005
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发表时间：
2005-03-01
影响因子：
5.3
通讯作者：
Canaani, E
中科院分区：
文献类型：
--
作者：
Krajewski, WA;Nakamura, T;Canaani, E
SET结构域在进化上是保守的，存在于许多真核细胞染色质相关蛋白中，包括三胸组（TrxG）和多梳组（PcG）的一些表观遗传转录调节因子和位置效应杂色修饰因子。所有SET域检查组蛋白赖氨酸甲基转移酶活性，暗示这些蛋白质的表观遗传标记的产生。然而，SET蛋白最初募集到靶基因的模式以及它们与基因的关联在复制后维持的方式尚不清楚。我们发现SET 1和SET 2家族的含SET蛋白在前SET区域或在前SET-SET和SET-后SET边界处含有非常紧密地结合单链DNA（ssDNA）和RNA的基序。这些基序还结合由超螺旋张力或在双链体DNA的体外转录期间产生的ssDNA片段。重要的是，这种结合能抵抗核小体组装，干扰规则核小体阵列的形成。SIUV 3 - 9 SET家族的两个代表SU（VAR）3-9和G9 a不结合ssDNA。trx（Z11）同源异型点突变位于TRX SET内，破坏胚胎发育，损害蛋白质的ssDNA结合能力。我们认为这里描述的基序可能直接参与SET蛋白的生物学功能。单链核酸的结合可能在蛋白质向靶基因的初始募集、DNA复制后维持它们的结合或维持单链构型的DNA延伸以允许连续转录中发挥作用。
The evolutionary conserved SET domain is present in many eukaryotic chromatin-associated proteins, including some members of the trithorax (TrxG) group and the polycomb (PcG) group of epigenetic transcriptional regulators and modifiers of position effect variegation. All SET domains examined exhibited histone lysine methyltransferase activity, implicating these proteins in the generation of epigenetic marks. However, the mode of the initial recruitment of SET proteins to target genes and the way that their association with the genes is maintained after replication are not known. We found that SET-containing proteins of the SET1 and SET2 families contain motifs in the pre-SET region or at the pre-SET-SET and SET-post-SET boundaries which very tightly bind single-stranded DNA (ssDNA) and RNA. These motifs also bind stretches of ssDNA generated by superhelicall tension or during the in vitro transcription of duplex DNA. Importantly, such binding withstands nucleosome assembly, interfering with the formation of regular nucleosomal arrays. Two representatives of the SIUV39 SET family, SU(VAR)3-9 and G9a, did not bind ssDNA. The trx(Z11) homeotic point mutation, which is located within TRX SET and disrupts embryonic development, impairs the ssDNA binding capacity of the protein. We suggest that the motifs described here may be directly involved in the biological function(s) of SET-containing proteins. The binding of single-stranded nucleic acids might play a role in the initial recruitment of the proteins to target genes, in the maintenance of their association after DNA replication, or in sustaining DNA stretches in a single-stranded configuration to allow for continuous transcription.