Long non-coding RNAs (lncRNAs) such as Mhrt (myosin heavy-chain-associated RNA transcripts) and Chaer (cardiac-hypertrophy-associated epigenetic regulator) have been shown to regulate the hypertrophic response through their interaction with chromatin-regulatory complexes. Mhrt binds the transcription activator BRG1 and prevents it from recognizing its genomic DNA targets. This releases the chromatin from its inhibitory conformation and facilitates the transcription of an antihypertrophic gene profile. Similarly, Chaer directly binds to polycomb repressive complex 2 (PRC2), releasing chromatin from a repressed state; however, this lncRNA enables the hypertrophic response, suggesting the activation of a hypertrophic gene profile. Me, methyl group; PARP, poly (ADP-ribose) polymerase; Pol II, RNA polymerase II; R, ribosyl group; SAM, S-adenosyl methionine.