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infection from secondary stripping. In brief, as a pluripotential medical dressing sensor, the HAP/SN-NR has a promising future in various applications, especially tissue repair.

Objectives Mixed lineage leukaemia protein‐1 (MLL1) mediates histone 3 lysine 4 (H3K4) trimethylation (me3) and plays vital roles during early embryonic development and hematopoiesis. In our previous study, we found its expression was positively correlated with embryonic myogenic ability in pigs, indicating its potential roles in mammalian muscle development. The present work aimed to explore the roles and regulation mechanisms of MLL1 in myogenesis. Materials and methods The expression of MLL1 in C2C12 cells was experimentally manipulated using small interfering RNAs (siRNA). 5‐ethynyl‐2′‐deoxyuridine (EdU) assay, cell cycle assay, immunofluorescence, qRT‐PCR and Western blot were performed to assess myoblast proliferation and differentiation. Chromatin immunoprecipitation assay was conducted to detect H3K4me3 enrichment on myogenic factor 5 (Myf5) promoter. A cardiotoxin (CTX)‐mediated muscle regeneration model was used to investigate the effects of MLL1 on myogenesis in vivo. Results MLL1 was highly expressed in proliferating C2C12 cells, and expression decreased after differentiation. Knocking down MLL1 suppressed myoblast proliferation and impaired myoblast differentiation. Furthermore, knockdown of MLL1 resulted in the arrest of cell cycle in G1 phase, with decreased expressions of Myf5 and Cyclin D1. Mechanically, MLL1 transcriptionally regulated Myf5 by mediating H3K4me3 on its promoter. In vivo data implied that MLL1 was required for Pax7‐positive satellite cell proliferation and muscle repair. Conclusion MLL1 facilitates proliferation of myoblasts and Pax7‐positive satellite cells by epigenetically regulating Myf5 via mediating H3K4me3 on its promoter.

Here, we performed whole‐genome bisulfite sequencing of longissimus dorsi muscle from Landrace and Wuzhishan (WZS) miniature pigs during 18, 21, and 28 d postcoitum. It was uncovered that in regulatory regions only around transcription start sites (TSSs), gene expression and methylation showed negative correlation, whereas in gene bodies, positive correlation occurred. Furthermore, earlier myogenic gene demethylation around TSSs and earlier hypermethylation of myogenic genes in gene bodies were considered to trigger their earlier expression in miniature pigs. Furthermore, by analyzing the methylation pattern of the myogenic differentiation 1(MyoD) promoter and distal enhancer, we found that earlier demethylation of the MyoD distal enhancer in WZSs contributes to its earlier expression. Moreover, DNA demethylase Tet1 was found to be involved in the demethylation of the myogenin promoter and promoted immortalized mouse myoblast cell line (C2C12) and porcine embryonic myogenic cell differentiation. This study reveals that earlier demethylation of myogenic genes contributes to precocious terminal differentiation of myoblasts in miniature pigs.—Zhang, X., Nie, Y., Cai, S., Ding, S., Fu, B., Wei, H., Chen, L., Liu, X., Liu, M., Yuan, R., Qiu, B., He, Z., Cong, P., Chen, Y., Mo, D. Earlier demethylation of myogenic genes contributes to embryonic precocious terminal differentiation of myoblasts in miniature pigs. FASEB J. 33, 9638–9655 (2019). http://www.fasebj.org

Myofibres (primary and secondary myofibre) are the basic structure of muscle and the determinant of muscle mass. To explore the skeletal muscle developmental processes from primary myofibres to secondary myofibres in pigs, we conducted an integrative three-dimensional structure of genome and transcriptomic characterization of longissimus dorsi muscle of pig from primary myofibre formation stage [embryonic Day 35 (E35)] to secondary myofibre formation stage (E80). In the hierarchical genomic structure, we found that 11.43% of genome switched compartment A/B status, 14.53% of topologically associating domains are changed intradomain interactions (D-scores) and 2,730 genes with differential promoter–enhancer interactions and (or) enhancer activity from E35 to E80. The alterations of genome architecture were found to correlate with expression of genes that play significant roles in neuromuscular junction, embryonic morphogenesis, skeletal muscle development or metabolism, typically, NEFL, MuSK, SLN, Mef2D and GCK. Significantly, Sox6 and MATN2 play important roles in the process of primary to secondary myofibres formation and increase the regulatory potential score and genes expression in it. In brief, we reveal the genomic reorganization from E35 to E80 and construct genome-wide high-resolution interaction maps that provide a resource for studying long-range control of gene expression from E35 to E80.