Methods are provided for the identification of compounds that selectively modulate epigenetic changes in gene expression. Compounds, compositions, kits or assays devices, and methods are provided for modulating the expression, endogenous levels or the function of small non-coding RNAs cognate to or transcribed by heterochromatic regions subject to epigenetic regulation (i.e., promoters, enhancers, centromeres, telomeres, origins of DNA replication, imprinted loci, or loci marked by dosage-compensation), and for modulating the formation or function of heterochromatin in cells, tissues or animals.