DNA-binding motif and target genes of the imprinted transcription factor PEG3.
DNA-binding motif and target genes of the imprinted transcription factor PEG3.
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DOI：
10.1016/j.gene.2012.10.005
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发表时间：
2013-01-10
期刊：
影响因子：
3.5
通讯作者：
Kim J
中科院分区：
文献类型：
--
作者：
Thiaville MM;Huang JM;Kim H;Ekram MB;Roh TY;Kim J
Peg3基因仅在位于小鼠7号染色体近端的父系遗传等位基因中表达。根据其多个锌指基序和核定位，预测由该印记基因编码的Peg3蛋白与DNA结合。在本研究中，我们通过鉴定PEG3‘S的结合基序和靶基因，证明了PEG3’PEG3‘与DNA的结合能力。通过染色质免疫沉淀分析，我们成功地从小鼠脑提取液中确定了Peg3结合的靶区。PEG3通过共同的DNA结合基序AGTnnCnnnTGGCT与这些候选区域结合。体外启动子分析证实，Peg3通过这个基序控制特定基因的表达。与这些观察结果一致的是，在Peg3蛋白水平降低的突变小鼠模型中，目标基因子集的转录水平也受到影响。总体而言，这些结果证实了Peg3是一种DNA结合蛋白，控制着参与不同细胞功能的特定靶基因。
The Peg3 gene is expressed only from the paternally inherited allele located on proximal mouse chromosome 7. The PEG3 protein encoded by this imprinted gene is predicted to bind DNA based on its multiple zinc finger motifs and nuclear localization. In the current study, we demonstrated PEG3’s DNA-binding ability by characterizing its binding motif and target genes. We successfully identified target regions bound by PEG3 from mouse brain extracts using chromatin immunoprecipitation analysis. PEG3 was demonstrated to bind these candidate regions through the consensus DNA-binding motif AGTnnCnnnTGGCT. In vitro promoter assays established that PEG3 controls the expression of a given gene through this motif. Consistent with these observations, the transcriptional levels of a subset of the target genes are also affected in a mutant mouse model with reduced levels of PEG3 protein. Overall, these results confirm PEG3 as a DNA-binding protein controlling specific target genes that are involved in distinct cellular functions.
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