Leyva-Díaz Eduardo, Stefanakis Nikolaos, Carrera Inés, Glenwinkel Lori, Wang Guoqiang, Driscoll Monica, Hobert Oliver
Departments of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, New York 10027 Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, New York 10027
Departments of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, New York 10027 Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, New York 10027.
Genetics. 2017 Oct;207(2):529-545. doi: 10.1534/genetics.117.300134. Epub 2017 Aug 11.
Repetitive DNA sequences are subject to gene silencing in various animal species. Under specific circumstances repetitive DNA sequences can escape such silencing. For example, exogenously added, extrachromosomal DNA sequences that are stably inherited in multicopy repetitive arrays in the nematode are frequently silenced in the germline, whereas such silencing often does not occur in the soma. This indicates that somatic cells might utilize factors that prevent repetitive DNA silencing. Indeed, such "antisilencing" factors have been revealed through genetic screens that identified mutant loci in which repetitive transgenic arrays are aberrantly silenced in the soma. We describe here a novel locus, (for protein containing ALS2CR12 signature), required to prevent silencing of repetitive transgenes in neurons and other somatic tissue types. deficiency also severely impacts animal vigor and confers phenotypes reminiscent of accelerated aging. We find that is a member of a large family of divergent genes (39 members), defined by homology to the ALS2CR12 protein family. While gene family members are highly divergent, they show striking patterns of chromosomal clustering. The family expansion appears -specific and has not occurred to the same extent in other nematode species for which genome sequences are available. The transgene-silencing phenotype observed upon loss of PALS-22 protein depends on the biogenesis of small RNAs. We speculate that the gene family may be part of a species-specific cellular defense mechanism.
重复DNA序列在各种动物物种中会发生基因沉默。在特定情况下，重复DNA序列可以逃避这种沉默。例如，外源添加的、在线虫中以多拷贝重复阵列稳定遗传的染色体外DNA序列在生殖系中经常被沉默，而在体细胞中这种沉默通常不会发生。这表明体细胞可能利用了防止重复DNA沉默的因子。事实上，通过遗传筛选已经揭示了这样的“抗沉默”因子，这些筛选鉴定出了突变位点，其中重复转基因阵列在体细胞中异常沉默。我们在此描述一个新的位点，（含ALS2CR12特征蛋白），它是防止神经元和其他体细胞组织类型中重复转基因沉默所必需的。PALS-22缺陷也严重影响动物活力，并赋予类似于加速衰老的表型。我们发现PALS-22是一个由与ALS2CR12蛋白家族同源性定义的大的发散基因家族（39个成员）的一员。虽然基因家族成员高度发散，但它们显示出明显的染色体聚类模式。该家族的扩张似乎是特定物种的，在其他有基因组序列的线虫物种中没有发生到相同程度。PALS-22蛋白缺失时观察到的转基因沉默表型取决于小RNA的生物合成。我们推测PALS-22基因家族可能是物种特异性细胞防御机制的一部分。
