The ciliated protozoan Tetrahymena thermophila undergoes extensive DNA elimination when the germline micronucleus produces the new somatic macronucleus during sexual reproduction. DNA elimination is epigenetically controlled by DNA sequences of the parental macronuclear genome and this epigenetic regulation is mediated by ~28-30 nucleotide small RNAs that are produced and operated by an RNAi-related mechanism. We have previously reported that small RNA-mediated comparison of the germline and somatic genomes underlies identification of the eliminated sequences. In addition, we recently found an additional layer of small RNA-mediated identification of the eliminated sequences. We found that a limited set of Internal Eliminated Sequences (IESs) containing potentially active TEs produces a class of small RNAs that recognize not only the IESs from which they are derived but also other IESs in trans. This trans-recognition triggers the expression of another class of small RNAs that identify other IESs. Therefore, TE-related sequences in Tetrahymena are robustly targeted for elimination by a genome-wide trans-recognition network accompanied by a chain reaction of small RNA production. In this presentation, I will discuss our latest picture of the small RNA-directed DNA elimination mechanism.