Department of Molecular, Cell and Developmental Biology and.
Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Proc Natl Acad Sci U S A. 2014 May 20;111(20):7474-9. doi: 10.1073/pnas.1406611111. Epub 2014 May 5.
Epigenetic gene silencing is of central importance to maintain genome integrity and is mediated by an elaborate interplay between DNA methylation, histone posttranslational modifications, and chromatin remodeling complexes. DNA methylation and repressive histone marks usually correlate with transcriptionally silent heterochromatin, however there are exceptions to this relationship. In Arabidopsis, mutation of Morpheus Molecule 1 (MOM1) causes transcriptional derepression of heterochromatin independently of changes in DNA methylation. More recently, two Arabidopsis homologues of mouse microrchidia (MORC) genes have also been implicated in gene silencing and heterochromatin condensation without altering genome-wide DNA methylation patterns. In this study, we show that Arabidopsis microrchidia (AtMORC6) physically interacts with AtMORC1 and with its close homologue, AtMORC2, in two mutually exclusive protein complexes. RNA-sequencing analyses of high-order mutants indicate that AtMORC1 and AtMORC2 act redundantly to repress a common set of loci. We also examined genetic interactions between AtMORC6 and MOM1 pathways. Although AtMORC6 and MOM1 control the silencing of a very similar set of genomic loci, we observed synergistic transcriptional regulation in the mom1/atmorc6 double mutant, suggesting that these epigenetic regulators act mainly by different silencing mechanisms.
表观遗传基因沉默对于维持基因组完整性至关重要，它是由 DNA 甲基化、组蛋白翻译后修饰和染色质重塑复合物之间的精细相互作用介导的。DNA 甲基化和抑制性组蛋白标记通常与转录沉默的异染色质相关，但这种关系也存在例外。在拟南芥中，Morpheus 分子 1（MOM1）的突变导致异染色质的转录去抑制，而与 DNA 甲基化的变化无关。最近，两种拟南芥类小鼠 microrchidia（MORC）基因的同源物也被牵连到基因沉默和异染色质浓缩中，而不会改变全基因组 DNA 甲基化模式。在这项研究中，我们表明拟南芥 microrchidia（AtMORC6）与 AtMORC1 及其紧密同源物 AtMORC2 相互作用，形成两种相互排斥的蛋白质复合物。高序突变体的 RNA-seq 分析表明，AtMORC1 和 AtMORC2 冗余地抑制一组共同的基因座。我们还研究了 AtMORC6 和 MOM1 途径之间的遗传相互作用。虽然 AtMORC6 和 MOM1 控制着非常相似的基因组基因座的沉默，但我们在 mom1/atmorc6 双突变体中观察到协同的转录调控，表明这些表观遗传调节剂主要通过不同的沉默机制发挥作用。
