Paramutation: epigenetic instructions passed across generations.
Paramutation: epigenetic instructions passed across generations.
复制标题
副突变：表观遗传指令代代相传。
作者：
Vicki L Chandler;Mary Alleman
异位突变是特定DNA序列进行反式交流以建立减数分裂可遗传表达状态的迷人能力。有趣的是，新沉默的序列继续向后代的幼稚等位基因发出指令。“副突变”一词最早由亚历山大·布林克于20世纪50年代提出，用于描述玉米r1基因座上的这一令人困惑的现象（布林克1956）;杂合子中特定等位基因之间的相互作用导致一个等位基因的基因表达可遗传地减少。不仅在减数分裂过程中，低表达的等位基因保持稳定的表达状态，而且在随后的世代中，低表达的等位基因可以诱导另一个高表达的等位基因沉默。这种变化的频率为100%，并且变化的稳定性低于典型的突变;因此称为“副突变”。几年后，小艾德科，描述了另一个玉米的例子，其中b1基因座上等位基因之间的相互作用也导致可遗传的沉默（Coe 1959），Rudolf Hagemann描述了番茄中sulfurea基因座上的相互作用（Hagemann 1969）。从那时起，在玉米和其他物种中也发现了副突变的其他例子（综述见钱德勒and Stam 2004; Stam and Mittelsten沙伊德2005;钱德勒2007），但最初描述副突变的两个玉米基因座r1和b1仍然是最广泛表征和最好理解的。r1和b1基因座编码密切相关的、功能等同的转录因子，这些转录因子激活花青素色素生物合成途径（Goff et al. 1990; Ludwig et al. 1990）。它们可能通过玉米进化过程中的古代异源四倍化事件导致的复制而彼此相关（Gaut和Doebley 1997）。这两个基因座具有多个等位基因，具有不同的表达模式，其调节发育期间花青素色素的分布（Styles et al. 1973; Coe 1979）。最近的研究表明，RNA在介导r1和b1副突变中发挥关键作用，因为编码RNA依赖性RNA聚合酶的mop 1基因（RDR;阿勒曼et al. 2006）是两个基因座副突变所必需的（Dorweiler et al. 2000）。然而，r1和b1副突变的性质存在显著差异，这暗示了不同的机制。在这篇文章中，最显着的差异R1和B1 paramutation的描述和潜在的机制进行了讨论，相对于我们目前的理解RNA干扰（RNAi）介导的转录沉默的作用。
PARAMUTATION is the fascinating ability of specific DNA sequences to communicate in trans to establish meiotically heritable expression states. Intriguingly, newly silenced sequences continue to issue instructions to naive alleles in subsequent generations. The term “paramutation” was first coined in the 1950s by Alexander Brink to describe this puzzling phenomenon at the r1 locus in maize (Brink 1956); an interaction between specific alleles in heterozygotes led to heritable decreases in gene expression of one allele. Not only was the reduced expression state stable through meiosis, but also the low-expressing allele could induce silencing of another high-expressing allele in subsequent generations. The frequency of the change was 100% and the stability of the change was lower than typical mutations; hence the term “paramutation.” A few years later, Ed Coe, Jr., described another maize example in which interaction between alleles at the b1 locus also led to heritable silencing (Coe 1959) and Rudolf Hagemann described interactions at the sulfurea locus in tomato (Hagemann 1969). Since that time other examples of paramutation have been identified in maize and in other species (reviewed in Chandler and Stam 2004; Stam and Mittelsten Scheid 2005; Chandler 2007), yet the two maize loci where paramutation was initially described, r1 and b1, remain the most extensively characterized and best understood. The r1 and b1 loci encode closely related, functionally equivalent transcription factors that activate the anthocyanin pigment biosynthetic pathway (Goff et al. 1990; Ludwig et al. 1990). They are likely related to each other through a duplication resulting from an ancient allotetraploidization event during maize evolution (Gaut and Doebley 1997). The two loci have multiple alleles with distinct expression patterns, which regulate the distribution of anthocyanin pigments during development (Styles et al. 1973; Coe 1979). Recent work demonstrates a key role for RNA in mediating both r1 and b1 paramutation, as the mop1 gene that encodes an RNA-dependent RNA polymerase (RDR; Alleman et al. 2006) is absolutely required for paramutation at both loci (Dorweiler et al. 2000). Yet, there are striking differences in the properties of r1 and b1 paramutation, which hint at distinct mechanisms. In this article, the most striking differences between r1 and b1 paramutation are described and potential mechanisms are discussed relative to our current understanding of the role of RNA interference (RNAi) in mediating transcriptional silencing.