Cam Hugh P, Noma Ken-ichi, Ebina Hirotaka, Levin Henry L, Grewal Shiv I S
Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892, USA.
Nature. 2008 Jan 24;451(7177):431-6. doi: 10.1038/nature06499. Epub 2007 Dec 19.
Transposable elements and their remnants constitute a substantial fraction of eukaryotic genomes. Host genomes have evolved defence mechanisms, including chromatin modifications and RNA interference, to regulate transposable elements. Here we describe a genome surveillance mechanism for retrotransposons by transposase-derived centromeric protein CENP-B homologues of the fission yeast Schizosaccharomyces pombe. CENP-B homologues of S. pombe localize at and recruit histone deacetylases to silence Tf2 retrotransposons. CENP-Bs also repress solo long terminal repeats (LTRs) and LTR-associated genes. Tf2 elements are clustered into 'Tf' bodies, the organization of which depends on CENP-Bs that display discrete nuclear structures. Furthermore, CENP-Bs prevent an 'extinct' Tf1 retrotransposon from re-entering the host genome by blocking its recombination with extant Tf2, and silence and immobilize a Tf1 integrant that becomes sequestered into Tf bodies. Our results reveal a probable ancient retrotransposon surveillance pathway important for host genome integrity, and highlight potential conflicts between DNA transposons and retrotransposons, major transposable elements believed to have greatly moulded the evolution of genomes.
转座元件及其残余部分在真核生物基因组中占相当大的比例。宿主基因组已经进化出防御机制,包括染色质修饰和RNA干扰,以调控转座元件。在这里,我们描述了一种由裂殖酵母粟酒裂殖酵母的转座酶衍生的着丝粒蛋白CENP - B同源物对逆转座子的基因组监测机制。粟酒裂殖酵母的CENP - B同源物定位于Tf2逆转座子并招募组蛋白去乙酰化酶使其沉默。CENP - Bs还抑制单独的长末端重复序列(LTRs)和与LTR相关的基因。Tf2元件聚集成“Tf”体,其组织依赖于显示离散核结构的CENP - Bs。此外,CENP - Bs通过阻止“灭绝”的Tf1逆转座子与现存的Tf2重组来防止其重新进入宿主基因组,并使隔离到Tf体中的Tf1整合体沉默并使其固定。我们的结果揭示了一条可能对宿主基因组完整性很重要的古老逆转座子监测途径,并突出了DNA转座子和逆转座子之间的潜在冲突,这两种主要的转座元件被认为极大地塑造了基因组的进化历程。