锌指蛋白ZNF644和WIZ通过调控G9a/GLP复合物来抑制基因表达。

The zinc finger proteins ZNF644 and WIZ regulate the G9a/GLP complex for gene repression.

作者信息

Bian Chunjing, Chen Qiang, Yu Xiaochun

机构信息

Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States.

出版信息

Elife. 2015 Mar 19;4:e05606. doi: 10.7554/eLife.05606.

The G9a/GLP complex mediates mono- and dimethylation of Lys9 of histone H3 at specific gene loci, which is associated with transcriptional repression. However, the molecular mechanism by which the G9a/GLP complex is targeted to the specific gene loci for H3K9 methylation is unclear. In this study, with unbiased protein affinity purification, we found ZNF644 and WIZ as two core subunits in the G9a/GLP complex. ZNF644 and WIZ interact with the transcription activation domain of G9a and GLP, respectively. Moreover, both ZNF644 and WIZ contain multiple zinc finger motifs that recognize consensus DNA sequences. ZNF644 and WIZ target G9a and GLP to the chromatin and mediate the G9a/GLP complex-dependent H3K9 methylation as well as gene repression. Thus, our studies reveal two key subunits in the G9a/GLP complex that regulate the function of this histone methyltransferase complex.

G9a/GLP复合物介导组蛋白H3赖氨酸9在特定基因位点的单甲基化和二甲基化，这与转录抑制相关。然而，G9a/GLP复合物靶向特定基因位点进行H3K9甲基化的分子机制尚不清楚。在本研究中，通过无偏差蛋白质亲和纯化，我们发现ZNF644和WIZ是G9a/GLP复合物中的两个核心亚基。ZNF644和WIZ分别与G9a和GLP的转录激活结构域相互作用。此外，ZNF644和WIZ都含有多个识别共有DNA序列的锌指基序。ZNF644和WIZ将G9a和GLP靶向染色质，并介导G9a/GLP复合物依赖性的H3K9甲基化以及基因抑制。因此，我们的研究揭示了G9a/GLP复合物中调节该组蛋白甲基转移酶复合物功能的两个关键亚基。