Chromatin Landscape During Skeletal Muscle Differentiation

Abstract

Cellular commitment and differentiation involve highly coordinated mechanisms by which tissue-specific genes are activated while others are repressed. These mechanisms rely on the activity of specific transcription factors, chromatin remodeling enzymes, and higherorder chromatin organization in order to modulate transcriptional regulation on multiple cellular contexts. Tissue-specific transcription factors are key mediators of cell fate specification with the ability to reprogram cell types into different lineages. A classic example of a master transcription factor is the muscle specific factor MyoD, which belongs to the family of myogenic regulatory factors (MRFs). MRFs regulate cell fate determination and terminal differentiation of the myogenic precursors in a multistep process that eventually culminate with formation of muscle fibers. This developmental progression involves the activation and proliferation of muscle stem cells, commitment, and cell cycle exit and fusion of mononucleated myoblast to generate myotubes and myofibers. Although the epigenetics of muscle regeneration has been extensively addressed and discussed over the recent years, the influence of higher-order chromatin organization in skeletal muscle regeneration is still a field of development. In this review, we will focus on the epigenetic mechanisms modulating muscle gene expression and on the incipient work that addresses three-dimensional genome architecture and its influence in cell fate determination and differentiation to achieve skeletal myogenesis. We will visit known alterations of genome organization mediated by chromosomal fusions giving rise to novel regulatory landscapes, enhancing oncogenic activation in muscle, such as alveolar rhabdomyosarcomas (ARMS).

Novel Tools and Investigative Approaches for the Study of Oligodendrocyte Precursor Cells (NG2-Glia) in CNS Development and Disease

“…The changing chromatin landscape has also been analyzed during OPC differentiation (Castelo-Branco and Liu, 2020 ) and mutations in chromatin modifiers, such as CHD7 and CHD8, have a profound effect on the formation of OLs from OPCs (Marie et al, 2018 ). Given the now widespread appreciation of the relationship between chromatin status and differentiation in multiple tissues (for example in skeletal muscle; Hernández-Hernández et al, 2020 ), this is not a surprising finding, but it nevertheless underscores epigenetic regulation as another field of ongoing research regarding OPCs (Gregath and Lu, 2018 ).…”

Combination of cell signaling molecules can facilitate MYOD1-mediated myogenic transdifferentiation of pig fibroblasts

“…Previously, numerous attempts have been made to reprogram non-muscle cells into skeletal muscle by modulating the expression of the transcription factor Myod1, which plays an important role in myogenesis [ 10 , 11 ]. 5-azacytidine (5-aza), a DNA methyltransferase inhibitor, induces demethylation of the Myod1 locus in differentiated somatic cells and increases Myod1 transcripts, leading to transdifferentiation into the myogenic lineage [ 9 , 36 ].…”

“…In addition to the basic region, the HLH motif of Myod1 is also required for myogenesis because the HLH motif dimerizes with other bHLH proteins, whose basic domains are involved in E-box binding [ 42 ]. The other domains are also highly conserved and have been known to be functional Myod1 domains [ 11 , 44 ]. For example, the acidic domain acts as a transcriptional activation domain (TAD) through additional DNA binding near E boxes, and both the H/C and helix3 domains are involved in chromatin remodeling to allow active transcription of sequential myogenic genes.…”

“…Forced Myod1 expression converts cell fates into muscle, which is responsible for Myod1 functioning as a transcriptional and epigenetic regulator, leading to the activation of muscle-specific genes in a feed-forward manner [ 10 , 11 ]. Small molecules can be supplemented in culture conditions for Myod1/MYOD1 -overexpressing somatic cells to improve the efficacy of transdifferentiation.…”

Regulation of skeletal myogenesis in C2C12 cells through modulation of Pax7, MyoD, and myogenin via different low-frequency electromagnetic field energies

“…The most critical part of this process is the activation and proliferation of satellite cells [34]. Studies have found that continuous activation depletes satellite cells and stagnates skeletal muscle recovery [35,36]. LF-EMF has been proven…”