Myostatin Mutation Enhances Bovine Myogenic Differentiation through PI3K/AKT/mTOR Signalling via Removing DNA Methylation of RACK1
Myostatin (MSTN) is a negative regulator of skeletal muscle development and plays an important role in muscle development. Fluctuations in gene expression influenced by DNA methylation are critical for homeostatic responses in muscle. However, little is known about the mechanisms underlying this flu...
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MDPI AG
2022-12-01
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author | Yiping Zhao Xiaoxia Xia Qiaomeng Wang Debao Hu Linlin Zhang Xin Li Xiangbin Ding Hong Guo Yiwen Guo |
author_facet | Yiping Zhao Xiaoxia Xia Qiaomeng Wang Debao Hu Linlin Zhang Xin Li Xiangbin Ding Hong Guo Yiwen Guo |
author_sort | Yiping Zhao |
collection | DOAJ |
description | Myostatin (MSTN) is a negative regulator of skeletal muscle development and plays an important role in muscle development. Fluctuations in gene expression influenced by DNA methylation are critical for homeostatic responses in muscle. However, little is known about the mechanisms underlying this fluctuation regulation and myogenic differentiation of skeletal muscle. Here we report a genome-wide analysis of DNA methylation dynamics in bovine skeletal muscle myogenesis after myostatin editing. We show that, after myostatin editing, an increase in TETs (DNA demethylases) and a concomitant increase in the receptor for activated C kinase 1 (RACK1) control the myogenic development of skeletal muscle. Interestingly, enhancement of PI3K/AKT/mTOR signaling by RACK1 appears to be an essential driver of myogenic differentiation, as it was associated with an increase in myogenic differentiation marker factors (MyHC and MyoG) during muscle differentiation. Overall, our results suggest that loss of myostatin promotes the myogenic differentiation response in skeletal muscle by decreasing DNA methylation of RACK1. |
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language | English |
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spelling | doaj.art-5eeb00bd103946ec91f6a67a99f905542023-11-16T15:05:32ZengMDPI AGCells2073-44092022-12-011215910.3390/cells12010059Myostatin Mutation Enhances Bovine Myogenic Differentiation through PI3K/AKT/mTOR Signalling via Removing DNA Methylation of RACK1Yiping Zhao0Xiaoxia Xia1Qiaomeng Wang2Debao Hu3Linlin Zhang4Xin Li5Xiangbin Ding6Hong Guo7Yiwen Guo8College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300384, ChinaCollege of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300384, ChinaCollege of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300384, ChinaCollege of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300384, ChinaCollege of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300384, ChinaCollege of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300384, ChinaCollege of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300384, ChinaCollege of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300384, ChinaCollege of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300384, ChinaMyostatin (MSTN) is a negative regulator of skeletal muscle development and plays an important role in muscle development. Fluctuations in gene expression influenced by DNA methylation are critical for homeostatic responses in muscle. However, little is known about the mechanisms underlying this fluctuation regulation and myogenic differentiation of skeletal muscle. Here we report a genome-wide analysis of DNA methylation dynamics in bovine skeletal muscle myogenesis after myostatin editing. We show that, after myostatin editing, an increase in TETs (DNA demethylases) and a concomitant increase in the receptor for activated C kinase 1 (RACK1) control the myogenic development of skeletal muscle. Interestingly, enhancement of PI3K/AKT/mTOR signaling by RACK1 appears to be an essential driver of myogenic differentiation, as it was associated with an increase in myogenic differentiation marker factors (MyHC and MyoG) during muscle differentiation. Overall, our results suggest that loss of myostatin promotes the myogenic differentiation response in skeletal muscle by decreasing DNA methylation of RACK1.https://www.mdpi.com/2073-4409/12/1/59myostatinDNA methylationRACK1PI3K/AKT/mTOR signalingmyogenic differentiation |
spellingShingle | Yiping Zhao Xiaoxia Xia Qiaomeng Wang Debao Hu Linlin Zhang Xin Li Xiangbin Ding Hong Guo Yiwen Guo Myostatin Mutation Enhances Bovine Myogenic Differentiation through PI3K/AKT/mTOR Signalling via Removing DNA Methylation of RACK1 Cells myostatin DNA methylation RACK1 PI3K/AKT/mTOR signaling myogenic differentiation |
title | Myostatin Mutation Enhances Bovine Myogenic Differentiation through PI3K/AKT/mTOR Signalling via Removing DNA Methylation of RACK1 |
title_full | Myostatin Mutation Enhances Bovine Myogenic Differentiation through PI3K/AKT/mTOR Signalling via Removing DNA Methylation of RACK1 |
title_fullStr | Myostatin Mutation Enhances Bovine Myogenic Differentiation through PI3K/AKT/mTOR Signalling via Removing DNA Methylation of RACK1 |
title_full_unstemmed | Myostatin Mutation Enhances Bovine Myogenic Differentiation through PI3K/AKT/mTOR Signalling via Removing DNA Methylation of RACK1 |
title_short | Myostatin Mutation Enhances Bovine Myogenic Differentiation through PI3K/AKT/mTOR Signalling via Removing DNA Methylation of RACK1 |
title_sort | myostatin mutation enhances bovine myogenic differentiation through pi3k akt mtor signalling via removing dna methylation of rack1 |
topic | myostatin DNA methylation RACK1 PI3K/AKT/mTOR signaling myogenic differentiation |
url | https://www.mdpi.com/2073-4409/12/1/59 |
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