Telomeric position effect (TPE) refers to the ability of telomeres to repress the transcription of genes in their vicinity. Internal stretches of C(1-3)A DNA, the sequence found at Saccharomyces telomeres, also repressed transcription of nearby genes. This repression, hereafter called C(1-3)A-based silencing, was observed at several chromosomal loci, including on a circular chromosome. The magnitude of C(1-3)A-based silencing was increased by both proximity to a telomere and increased length of the C(1-3)A tracts. C(1-3)A-based silencing was affected by many of the same genes and conditions that influence TPE and acted in an orientation-independent manner. Thus, in yeast, an expanded array of a simple repetitive DNA, C(1-3)A, is sufficient to promote the assembly of a transcriptionally silent chromosomal domain.