X inactive-specific transcript () is a long noncoding RNA that plays an essential role in X chromosome inactivation. Although RNA, like common protein-coding mRNAs, is transcribed by RNA polymerase II, spliced and polyadenylated, it is retained in the nucleus and associates with the X chromosome it originates from. It has been assumed that RNA recruits proteins involved in epigenetic modifications and chromatin compaction to the X chromosome. One of the major proteins constituting the nuclear matrix, hnRNP U, has been shown to be required for the association of RNA with the inactive X chromosome (Xi). In this study, we found that the first 950-nt sequence of RNA had the potential to associate with chromatin in a manner independent of hnRNP U. Furthermore, its chromatin association is apparently dependent on the presence of an intact A-repeat sequence, which is one of the repeats in / RNA conserved among many mammalian species, and has been shown to be important for RNA-mediated silencing. Taking this unexpected finding and a previous study demonstrating the effect of RNA lacking the A-repeat on the formation of the silent heterochromatin domain together, we suggest that the A-repeat captures chromatin near the initial loading site of RNA and relocates it into the core of the heterochromatin domain.
To produce muscle fibers for cultured meat on a large scale, it is important to expand myoblasts in a serum-reduced or serum-free medium to avoid cost, ethical, and environmental issues. Myoblasts such as C2C12 cells differentiate quickly into myotubes and lose their ability to proliferate when the serum-rich medium is replaced with a serum-reduced medium. This study demonstrates that Methyl-β-cyclodextrin (MβCD), a starch-derived agent that depletes cholesterol, can inhibit further differentiation of myoblasts at the MyoD-positive stage by reducing plasma membrane cholesterol on C2C12 cells and primary cultured chick muscle cells. Furthermore, MβCD efficiently blocks cholesterol-dependent apoptotic cell death of myoblasts, which is one of the mechanisms by which it inhibits the differentiation of C2C12 myoblast cells, as dead cells of myoblast are necessary for the fusion of adjacent myoblasts during the differentiation process into myotubes. Importantly, MβCD maintains the proliferative capacity of myoblasts only under differentiation conditions with a serum-reduced medium, suggesting that its mitogenic effect is due to its inhibitory effect on myoblast differentiation into myotube. In conclusion, this study provides significant insights into ensuring the proliferative capacity of myoblasts in a future serum-free condition for cultured meat production.
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