Department of Plant Biology, University of Geneva, Geneva, Switzerland.
PLoS Genet. 2012 Feb;8(2):e1002484. doi: 10.1371/journal.pgen.1002484. Epub 2012 Feb 9.
Shifts between epigenetic states of transcriptional activity are typically correlated with changes in epigenetic marks. However, exceptions to this rule suggest the existence of additional, as yet uncharacterized, layers of epigenetic regulation. MOM1, a protein of 2,001 amino acids that acts as a transcriptional silencer, represents such an exception. Here we define the 82 amino acid domain called CMM2 (Conserved MOM1 Motif 2) as a minimal MOM1 fragment capable of transcriptional regulation. As determined by X-ray crystallography, this motif folds into an unusual hendecad-based coiled-coil. Structure-based mutagenesis followed by transgenic complementation tests in plants demonstrate that CMM2 and its dimerization are effective for transcriptional suppression at chromosomal loci co-regulated by MOM1 and the siRNA pathway but not at loci controlled by MOM1 in an siRNA-independent fashion. These results reveal a surprising separation of epigenetic activities that enable the single, large MOM1 protein to coordinate cooperating mechanisms of epigenetic regulation.
转录活性的表观遗传状态之间的转变通常与表观遗传标记的变化相关。然而,这一规则的例外情况表明存在其他尚未被描述的表观遗传调控层次。MOM1 是一种 2001 个氨基酸的蛋白质,作为转录沉默子,就是这样一个例外。在这里,我们将一个被称为 CMM2(Conserved MOM1 Motif 2)的 82 个氨基酸的结构域定义为一个能够进行转录调控的最小 MOM1 片段。通过 X 射线晶体学确定,这个基序折叠成一个不寻常的基于十一肽的卷曲螺旋。基于结构的诱变,随后在植物中的转基因互补测试表明,CMM2 及其二聚体对于由 MOM1 和 siRNA 通路共同调控的染色质基因座的转录抑制是有效的,但对于不依赖于 siRNA 的 MOM1 调控的基因座则没有效果。这些结果揭示了一种惊人的表观遗传活性分离,使单个大型 MOM1 蛋白能够协调合作的表观遗传调控机制。