A long noncoding RNA, <i>LncMyoD</i> , modulates chromatin accessibility to regulate muscle stem cell myogenic lineage progression

Abstract

Epigenetics regulation plays a critical role in determining cell identity by controlling the accessibility of lineage-specific regulatory regions. In muscle stem cells, epigenetic mechanisms of how chromatin accessibility is modulated during cell fate determination are not fully understood. Here, we identified a long noncoding RNA, <i>LncMyoD</i>, that functions as a chromatin modulator for myogenic lineage determination and progression. The depletion of <i>LncMyoD</i> in muscle stem cells led to the down-regulation of myogenic genes and defects in myogenic differentiation. <i>LncMyoD</i> exclusively binds with MyoD and not with other myogenic regulatory factors and promotes transactivation of target genes. The mechanistic study revealed that loss of <i>LncMyoD</i> prevents the establishment of a permissive chromatin environment at myogenic E-box-containing regions, therefore restricting the binding of MyoD. Furthermore, the depletion of <i>LncMyoD</i> strongly impairs the reprogramming of fibroblasts into the myogenic lineage. Taken together, our study shows that <i>LncMyoD</i> associates with MyoD and promotes myogenic gene expression through modulating MyoD accessibility to chromatin, thereby regulating myogenic lineage determination and progression.