A long non-coding RNA, LncMyoD, regulates skeletal muscle differentiation through modulating chromatin accessibility

Epigenetics is the study of heritable changes in gene expression, i.e., active versus inactive genes, that do not involve alterations in the DNA sequence. Unlike genetic changes, epigenetic modifications are reversible and play an essential role in determining how your cells read a DNA sequence. One example of epigenetic regulation is controlling how accessible DNA is to proteins such as transcription factors, which help turn specific genes “on” or “off” by binding to nearby DNA. In the cell nucleus, DNA is packaged in a particular form known as chromatins, consisting of DNA and histones. By changing chromatin accessibility, our cells can control which genes are accessible to transcription factors and regulate gene expression.

Long noncoding RNAs (lncRNAs) are transcripts >200 nucleotides with no protein-coding ability and play critical roles in biological processes such as muscle development and differentiation. However, it is unclear how lncRNAs control muscle stem cells to become functional muscle cells through the myogenic lineage. In this study published in the journal PNAS, Prof. Tom Cheung and his research team have found that a lncRNA, namely LncMyoD, regulates the differentiation of muscle cells through modulating chromatin accessibility.

The team has discovered extensive changes in chromatin accessibility during muscle stem cell (also known as satellite cell) activation and identified LncMyoD as an essential factor in satellite cell activation and differentiation using loss-of-function experiments. The research team then determined that LncMyoD functions by directly binding to MyoD, a myogenic transcription factor, making it easier to bind to DNA and also by opening up the myogenic region of the chromatin for cells to enter the myogenic differentiation. Also, in the presence of MyoD, LncMyoD is capable of reprogramming fibroblasts (cells of connective tissue) into myoblasts (early muscle cells).

Journal Reference:

Dong A, Preusch CB, So WK, Lin K, Luan S, Yi R, Wong JW, Wu Z, Cheung TH. A long noncoding RNA, LncMyoD, modulates chromatin accessibility to regulate muscle stem cell myogenic lineage progression. Proc Natl Acad Sci U S A. 2020 Dec 22;117(51):32464-32475. doi: 10.1073/pnas.2005868117.