Department of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, Terasaki Life Sciences Building, 610 Charles Young Drive East, Los Angeles, CA 90095-723905, USA.
Science. 2012 Jun 15;336(6087):1448-51. doi: 10.1126/science.1221472. Epub 2012 May 3.
Transposable elements (TEs) and DNA repeats are commonly targeted by DNA and histone methylation to achieve epigenetic gene silencing. We isolated mutations in two Arabidopsis genes, AtMORC1 and AtMORC6, which cause derepression of DNA-methylated genes and TEs but no losses of DNA or histone methylation. AtMORC1 and AtMORC6 are members of the conserved Microrchidia (MORC) adenosine triphosphatase (ATPase) family, which are predicted to catalyze alterations in chromosome superstructure. The atmorc1 and atmorc6 mutants show decondensation of pericentromeric heterochromatin, increased interaction of pericentromeric regions with the rest of the genome, and transcriptional defects that are largely restricted to loci residing in pericentromeric regions. Knockdown of the single MORC homolog in Caenorhabditis elegans also impairs transgene silencing. We propose that the MORC ATPases are conserved regulators of gene silencing in eukaryotes.
转座元件 (TEs) 和 DNA 重复序列通常是 DNA 和组蛋白甲基化的靶标,以实现表观遗传基因沉默。我们分离了两个拟南芥基因 AtMORC1 和 AtMORC6 的突变,这些突变导致 DNA 甲基化基因和 TE 的去抑制,但不会导致 DNA 或组蛋白甲基化的丢失。AtMORC1 和 AtMORC6 是保守的 Microrchidia (MORC) 三磷酸腺苷酶 (ATPase) 家族的成员,该家族被预测能够催化染色体超结构的改变。atmorc1 和 atmorc6 突变体显示着丝粒周围异染色质的去凝聚,着丝粒区域与基因组其余部分的相互作用增加,以及转录缺陷,这些缺陷主要局限于位于着丝粒区域的基因座。在秀丽隐杆线虫中敲低单个 MORC 同源物也会损害转基因沉默。我们提出,MORC ATPases 是真核生物中基因沉默的保守调节剂。