In collaboration with investigators from other institutions, we identify a novel long non-coding RNA (lncRNA), a form of RNA that does not make proteins, in mouse hearts that protects the heart from hypertrophy and heart failure. We first identified a cluster of lncRNA transcripts between two contractile myosin motor genes, Myh6 (α-MHC) and Myh7 (β-MHC) in hearts, and named them MyHEART genes. Among this cluster of MyHEART lncRNA genes, we show that restoring the expression level of MyHEART-779 protects the mouse hearts from hypertrophy and dysfunction. We further show that MyHEART-779 prevents Brg1 (a transcription regulator) from targeting to the promoters of downstream genes of Brg1 by binding to the active helicase core of Brg1, resulting in the down-regulation of pro-hypertrophic effects of Brg1. This inhibitory interaction of MyHEART on Brg1 function is a novel mechanism for how an lncRNA can regulate chromatin function. Our study also establishes a new paradigm in the biochemical basis of how lncRNA antagonizes chromatin regulators to gain control over the chromatin. These new mechanisms regarding how Brg1 recognizes target chromatins are novel and have never been observed or conceived by others working in this field. We believe that these novel mechanisms of lncRNA actions might extend beyond cardiac biology and are applicable to the general area of biology.