A long noncoding RNA, LncMyoD , 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,LncMyoD, that functions as a chromatin modulator for myogenic lineage determination and progression. The depletion ofLncMyoDin muscle stem cells led to the down-regulation of myogenic genes and defects in myogenic differentiation.LncMyoDexclusively binds with MyoD and not with other myogenic regulatory factors and promotes transactivation of target genes. The mechanistic study revealed that loss ofLncMyoDprevents the establishment of a permissive chromatin environment at myogenic E-box–containing regions, therefore restricting the binding of MyoD. Furthermore, the depletion ofLncMyoDstrongly impairs the reprogramming of fibroblasts into the myogenic lineage. Taken together, our study shows thatLncMyoDassociates with MyoD and promotes myogenic gene expression through modulating MyoD accessibility to chromatin, thereby regulating myogenic lineage determination and progression.

SAFA facilitates chromatin opening of immune genes through interacting with nascent antiviral RNAs

“…Recent studies have shown that RNAs produced during early steps in transcription initiated the transcriptional condensate formation (Henninger et al, 2021). Moreover, the regulation roles of RNAs in gene expression showed locus-specific characteristics, which tends to regulate the expression of adjacent or related genes (Dong et al, 2020; Gendrel and Heard, 2014; Mousavi et al, 2013; Rinn et al, 2007). The RNA binding-dependent regulatory activity of SAFA, coupled with evidence that the associated RNAs are mainly antiviral innate immunity related, led us to wonder whether the SAFA-interacting RNA mapped or characterized the regulatory regions of accessible chromatin during viral infection.…”

“…By using genome-wide binding profiling, Kambiz et al showed that eRNAs regulate genomic accessibility of the transcriptional complex to defined regulatory regions (Mousavi et al, 2013). Dong et al reported that the lncRNA, LncMyoD , regulates lineage determination and progression through modulating chromatin accessibility (Dong et al, 2020). Our previous results suggest that SAFA facilitates anti-viral innate immune responses, which is also dependent on the RNA-binding ability (Cao et al, 2019a).…”

“…Processes involved in the alteration of chromatin accessibility are diverse, including post-translational modifications of histones, incorporation of histone variants, DNA methylation and ATP-dependent chromatin remodeling (Bao et al, 2019; Deuring et al, 2000; Govin et al, 2004; Venkatesh and Workman, 2015). There is accumulating evidence indicating that RNAs also play an important role (Caudron-Herger and Rippe, 2012; Dong et al, 2020; Gupta et al, 2010; Han and Chang, 2015; Mousavi et al, 2013). The RNA encoded by HOXC locus represses transcription of the HOXD locus through interacting with the polycomb repressive complex 2 (PRC2) (Rinn et al, 2007).…”

An Analysis of Differentially Expressed Coding and Long Non-Coding RNAs in Multiple Models of Skeletal Muscle Atrophy

“…Recently, Li et al found that the lncRNA MSTRG.42019 was associated with skeletal muscle fiber-type switching in pigs [53]. Several lncRNAs, such as LncMyoD, SAM, H19, and CTTN-IT1, affect the activity of satellite cells in mice, pigs, and sheep [54][55][56][57]. The in vivo silencing of Pvt1 results in increases in the size and number of mitochondria [20].…”

Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis

“…For instance, HOTAIR (HOX transcript antisense intergenic RNA), a well-known lncRNA localized both in the cytoplasm and nucleus, could modulate chromatin accessibility by serving as a scaffold for the PRC2 subunit EZH2, or act also at the posttranscriptional level by sponging several miRNAs[ 31 , 32 ]. In a manner similar to HOTAIR, FER1L4 may also interact with chromatin and then recruit protein complexes to remodel chromatin states, thus causing manifest changes in gene expression and gene regulatory network[ 33 , 34 ]. However, it needs further experimental confirmation.…”