PLU-1 is an H3K4 dernethylase involved in transcriptional repression and breast cancer cell proliferation
PLU-1 is an H3K4 dernethylase involved in transcriptional repression and breast cancer cell proliferation
复制标题
DOI：
10.1016/j.molcel.2007.03.001
复制
发表时间：
2007-03-23
期刊：
影响因子：
16
通讯作者：
Zhang, Yi
中科院分区：
文献类型：
--
作者：
Yamane, Kenichi;Tateishi, Keisuke;Zhang, Yi
通过组蛋白甲基化对染色质的翻译后修饰对核功能具有广泛的影响，包括转录调控、基因组完整性的维持和表观遗传。用于放置组蛋白甲基化标记的酶已得到很好的表征，但组蛋白去甲基化系统的身份直到最近仍然难以捉摸。组蛋白脱甲基酶能够直接从修饰的赖氨酸残基上去除甲基，这证明组蛋白甲基化是一种动态修饰。迄今为止鉴定的最广泛的组蛋白去甲基化酶家族包含JmjC结构域并通过羟基化反应催化去甲基化。在这里，我们确定PLU-1，一种与乳腺癌有关的转录抑制因子，作为一种组蛋白脱甲基酶，具有逆转三甲基H3 K4修饰状态的能力。此外，我们发现PLU-1介导的H3 K4脱甲基酶活性通过抑制肿瘤抑制基因（包括BRCA 1）在乳腺癌细胞的增殖能力中起着重要作用。
Posttranslational modification of chromatin by histone methylation has wide-ranging effects on nuclear function, including transcriptional regulation, maintenance of genome integrity, and epigenetic inheritance. The enzymes utilized to place histone methylation marks are well characterized, but the identity of a histone demethylation system remained elusive until recently. The discovery of histone demethylase enzymes capable of directly removing methyl groups from modified lysine residues has demonstrated that histone methylation is a dynamic modification. The most extensive family of histone demethylase enzymes identified so far contains a JmjC domain and catalyzes demethylation through a hydroxylation reaction. Here, we identify PLU-1, a transcriptional repressor implicated in breast cancer, as a histone demethylase enzyme that has the ability to reverse the trimethyl H3K4 modification state. Furthermore, we reveal that PLU-1-mediated H3K4 demethylase activity plays an important role in the proliferative capacity of breast cancer cells through repression of tumor suppressor genes, including BRCA1.