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

First Author  Dong A Year  2020
Journal  Proc Natl Acad Sci U S A Volume  117
Issue  51 Pages  32464-32475
PubMed ID  33293420 Mgi Jnum  J:300951
Mgi Id  MGI:6492045 Doi  10.1073/pnas.2005868117
Citation  Dong A, et al. (2020) A long noncoding RNA, LncMyoD, modulates chromatin accessibility to regulate muscle stem cell myogenic lineage progression. Proc Natl Acad Sci U S A 117(51):32464-32475
abstractText  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, LncMyoD, that functions as a chromatin modulator for myogenic lineage determination and progression. The depletion of LncMyoD in muscle stem cells led to the down-regulation of myogenic genes and defects in myogenic differentiation. LncMyoD exclusively binds with MyoD and not with other myogenic regulatory factors and promotes transactivation of target genes. The mechanistic study revealed that loss of LncMyoD prevents the establishment of a permissive chromatin environment at myogenic E-box-containing regions, therefore restricting the binding of MyoD. Furthermore, the depletion of LncMyoD strongly impairs the reprogramming of fibroblasts into the myogenic lineage. Taken together, our study shows that LncMyoD associates with MyoD and promotes myogenic gene expression through modulating MyoD accessibility to chromatin, thereby regulating myogenic lineage determination and progression.
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