PT - JOURNAL ARTICLE AU - Leyva-Díaz, Eduardo AU - Stefanakis, Nikolaos AU - Carrera, Inés AU - Glenwinkel, Lori AU - Wang, Guoqiang AU - Driscoll, Monica AU - Hobert, Oliver TI - Silencing of Repetitive DNA Is Controlled by a Member of an Unusual <em>Caenorhabditis elegans</em> Gene Family AID - 10.1534/genetics.117.300134 DP - 2017 Oct 01 TA - Genetics PG - 529--545 VI - 207 IP - 2 4099 - http://www.genetics.org/content/207/2/529.short 4100 - http://www.genetics.org/content/207/2/529.full SO - Genetics2017 Oct 01; 207 AB - 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 Caenorhabditis elegans 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, pals-22 (for protein containing ALS2CR12 signature), required to prevent silencing of repetitive transgenes in neurons and other somatic tissue types. pals-22 deficiency also severely impacts animal vigor and confers phenotypes reminiscent of accelerated aging. We find that pals-22 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 C. elegans-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 pals gene family may be part of a species-specific cellular defense mechanism.