A component of the transcriptional repressor MeCP1 shares a motif with DNA methyltransferase and HRX proteins
A component of the transcriptional repressor MeCP1 shares a motif with DNA methyltransferase and HRX proteins
复制标题
DOI：
10.1038/ng0797-256
复制
发表时间：
1997-07-01
期刊：
影响因子：
30.8
通讯作者：
Bird, A
中科院分区：
文献类型：
--
作者：
Cross, SH;Meehan, RR;Bird, A
CpG 序列中胞嘧啶的甲基化对于小鼠发育至关重要 1，并且与脊椎动物系统中的转录抑制相关2。甲基 CpG 结合蛋白 (MeCP) 1 和 2 优先与甲基化 DNA 结合，并可抑制转录 3-6。 MeCP2 基因已被克隆，并且其中的甲基 CpG 结合域 (MBD) 已被定义7。对具有 MBD 序列的 DNA 序列数据库进行搜索，鉴定出具有编码 MBD 样区域潜力的人类 cDNA。完整 cDNA 的测序表明，开放阅读框还编码两个富含半胱氨酸的结构域，这些结构域存在于动物 DNA 甲基转移酶 (DNMT) 和哺乳动物 HRX 蛋白（也称为 MIL 和 ALL-1）8 中。 HRX 与果蝇 trithorax9,10 相关。这种蛋白质被称为ProteinContainingMBD(PCM1)，在细菌中表达，并被证明可以与甲基化DNA特异性结合。 PCM1 还以甲基化依赖性方式抑制体外转录。针对该蛋白质产生的多克隆抗体能够“超移”HeLa 细胞中的天然 MeCP1 复合物，表明 PCM1 是哺乳动物 MeCP1 的组成部分。
Methylation of cytosines within the sequence CpG is essential for mouse development1and has been linked to transcriptional suppression in vertebrate systems2. Methyl-CpG binding proteins (MeCPs) 1 and 2 bind preferentially to methylated DNA and can inhibit transcription3–6. The gene for MeCP2 has been cloned and a methyl-CpG binding domain (MBD) within it has been defined7. A search of DNA sequence databases with the MBD sequence identified a human cDNA with potential to encode an MBD-like region. Sequencing of the complete cDNA revealed that the open reading frame also encodes two cysteine-rich domains that are found in animal DNA methyltransferases (DNMTs) and in the mammalian HRX protein (also known as MIL and ALL-1)8. HRX is related toDrosophila trithorax9,10. The protein, known asProteinContainingMBD(PCM1), was expressed in bacteria and shown to bind specifically to methylated DNA. PCM1 also repressed transcriptionin vitroin a methylation-dependent manner. A poly-clonal antibody raised against the protein was able to ‘supershift’ the native MeCP1 complex from HeLa cells, indicating that PCM1 is a component of mammalian MeCP1.