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...

Full description

Bibliographic Details
Main Authors: Yiping Zhao, Xiaoxia Xia, Qiaomeng Wang, Debao Hu, Linlin Zhang, Xin Li, Xiangbin Ding, Hong Guo, Yiwen Guo
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/12/1/59
_version_ 1827760916707409920
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.
first_indexed 2024-03-11T10:05:50Z
format Article
id doaj.art-5eeb00bd103946ec91f6a67a99f90554
institution Directory Open Access Journal
issn 2073-4409
language English
last_indexed 2024-03-11T10:05:50Z
publishDate 2022-12-01
publisher MDPI AG
record_format Article
series Cells
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
work_keys_str_mv AT yipingzhao myostatinmutationenhancesbovinemyogenicdifferentiationthroughpi3kaktmtorsignallingviaremovingdnamethylationofrack1
AT xiaoxiaxia myostatinmutationenhancesbovinemyogenicdifferentiationthroughpi3kaktmtorsignallingviaremovingdnamethylationofrack1
AT qiaomengwang myostatinmutationenhancesbovinemyogenicdifferentiationthroughpi3kaktmtorsignallingviaremovingdnamethylationofrack1
AT debaohu myostatinmutationenhancesbovinemyogenicdifferentiationthroughpi3kaktmtorsignallingviaremovingdnamethylationofrack1
AT linlinzhang myostatinmutationenhancesbovinemyogenicdifferentiationthroughpi3kaktmtorsignallingviaremovingdnamethylationofrack1
AT xinli myostatinmutationenhancesbovinemyogenicdifferentiationthroughpi3kaktmtorsignallingviaremovingdnamethylationofrack1
AT xiangbinding myostatinmutationenhancesbovinemyogenicdifferentiationthroughpi3kaktmtorsignallingviaremovingdnamethylationofrack1
AT hongguo myostatinmutationenhancesbovinemyogenicdifferentiationthroughpi3kaktmtorsignallingviaremovingdnamethylationofrack1
AT yiwenguo myostatinmutationenhancesbovinemyogenicdifferentiationthroughpi3kaktmtorsignallingviaremovingdnamethylationofrack1