The RING finger/B-box factor TAM-1 and a retinoblastoma-like protein LIN-35 modulate context-dependent gene silencing in Caenorhabditis elegans
The RING finger/B-box factor TAM-1 and a retinoblastoma-like protein LIN-35 modulate context-dependent gene silencing in Caenorhabditis elegans
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DOI：
10.1101/gad.13.22.2958
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发表时间：
1999-11-15
影响因子：
10.5
通讯作者：
Fire, A
中科院分区：
文献类型：
--
作者：
Hsieh, J;Liu, J;Fire, A
背景依赖性基因沉默被许多生物体用于稳定调节大染色体区域的基因活性。我们已经使用串联阵列转基因作为模式基板中的秀丽隐杆线虫突变体，影响体细胞组织中的上下文依赖性基因沉默的屏幕。这个筛选产生了一个以前没有特征的基因的多个等位基因，命名为tam-1（串联阵列修饰）。tam-1的功能缺失突变导致许多高度重复的转基因的活性显著降低。这些影响显然是上下文依赖性的，因为非重复性转基因在tam-1突变背景中保留活性。除了转基因活性的显著改变外，tam-1突变体还表现出内源性细胞基因亚组表达的适度改变。这些效应包括将tam-1置于称为B类synMuv基因（对于合成多叶型表型）的组中的遗传相互作用;该家族在C.优美的B类synMuv家族其他成员的功能丧失突变体，包括lin-35，它编码一种类似于肿瘤抑制基因Rb的蛋白质，在体细胞转基因中表现出类似于tam-1突变体的超沉默。分子生物学分析表明，tam-1编码一种广泛表达的核蛋白，具有RING指和B-box基序。
Context-dependent gene silencing is used by many organisms to stably modulate gene activity for large chromosomal regions. We have used tandem array transgenes as a model substrate in a screen for Caenorhabditis elegans mutants that affect context-dependent gene silencing in somatic tissues. This screen yielded multiple alleles of a previously uncharacterized gene, designated tam-1 (for tandem-array-modifier). Loss-of-function mutations in tam-1 led to a dramatic reduction in the activity of numerous highly repeated transgenes. These effects were apparently context dependent, as nonrepetitive transgenes retained activity in a tam-1 mutant background. In addition to the dramatic alterations in transgene activity, tam-1 mutants showed modest alterations in expression of a subset of endogenous cellular genes. These effects include genetic interactions that place tam-1 into a group called the class B synMuv genes (for a Synthetic Multivulva phenotype); this family plays a negative role in the regulation of RAS pathway activity in C. elegans. Loss-of-function mutants in other members of the class-B synMuv family, including lin-35, which encodes a protein similar to the tumor suppressor Rb, exhibit a hypersilencing in somatic transgenes similar to that of tam-1 mutants. Molecular analysis reveals that tam-1 encodes a broadly expressed nuclear protein with RING finger and B-box motifs.