Integrative Analysis of Chromatin Accessibility and Transcriptional Landscape Identifies Key Genes During Muscle Development in Pigs

被引：0
作者：
Zhang, Dongjie [1 ]
Zhang, Qian [2 ]
Wu, Xiaoxu [2 ]
Wang, Liang [1 ]
Zhang, Xiaohan [2 ]
Liu, Di [1 ]
Yang, Xiuqin [2 ]
机构：
[1] Heilongjiang Acad Agr Sci, Inst Anim Husb, Harbin 150086, Peoples R China
[2] Northeast Agr Univ, Coll Anim Sci & Technol, Harbin 150030, Peoples R China
来源：
CELLS | 2024年 / 13卷 / 24期
基金：
中国国家自然科学基金;
关键词：
skeletal muscle; ATAC-seq; RNA-seq; transcription factor; dual-luciferase reporter analysis; SKELETAL-MUSCLE; EXPRESSION; MYOGENIN; NEURONS; GROWTH; RNA; DIFFERENTIATION; GENERATION; CONVERSION; PROTEINS;
D O I：
10.3390/cells13242118
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Many efforts have been made to reveal the mechanisms underlying skeletal muscle development because of its importance in animals. However, knowledge on chromatin accessibility, a prerequisite for gene expression, remains limited. Here, dynamic changes in chromatin accessibility were analyzed in the skeletal muscles of Min pigs at the ages of 30, 90, and 210 d using an assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). A total of 16,301 differentially accessible regions (DARs) associated with 7455 genes were identified among three developmental stages. Seven out of eight DARs selected for a functional analysis were found to regulate reporter gene expression significantly (p < 0.05), indicating that DARs are active in gene expression. A total of 2219 differentially expressed genes (DEGs) were identified with RNA sequencing (RNA-seq). Through integrated analyses of ATAC-seq and RNA-seq data, 54 DEG_DAR_genes and 61 transcription factors (TFs) were characterized as critical for muscle development. Among them, Kruppel-like factor 5 (KLF5), targeted to 36 DEG_DAR_genes, was the most important TF. The effects of KLF5 on DEG_DAR_gene expression were then analyzed with molecular biology techniques. KLF5 was found to regulate SLPI (secretory leukocyte proteinase inhibitor) expression by directly binding to the promoter; KLF5 was also involved in APOA1 (apolipoprotein A-I) expression through affecting the regulatory role of DAR located in the intron. These results indicate that the TFs identified were functional. Altogether, the chromatin accessibility region, TFs, and genes important for muscle development in Min pigs were identified. The results provide novel data for further revealing the mechanisms underlying the epigenetic regulation of muscle development.
引用
收藏
页数：17
相关论文
共 53 条
  • [1] Frontera W.R., Ochala J., Skeletal muscle: A brief review of structure and function, Calcif Tissue Int, 96, pp. 183-195, (2015)
  • [2] Mukund K., Subramaniam S., Skeletal muscle: A review of molecular structure and function, in health and disease, Wiley Interdiscip. Rev. Syst. Biol. Med, 12, (2020)
  • [3] Relaix F., Bencze M., Borok M.J., Der Vartanian A., Gattazzo F., Mademtzoglou D., Perez-Diaz S., Prola A., Reyes-Fernandez P.C., Rotini A., Et al., Perspectives on skeletal muscle stem cells, Nat. Commun, 12, (2021)
  • [4] Lagha M., Sato T., Bajard L., Daubas P., Esner M., Montarras D., Relaix F., Buckingham M., Regulation of skeletal muscle stem cell behavior by Pax3 and Pax7, Cold Spring Harb. Symp. Quant. Biol, 73, pp. 307-315, (2008)
  • [5] Taylor M.V., Hughes S.M., Mef2 and the skeletal muscle differentiation program, Semin. Cell Dev. Biol, 72, pp. 33-44, (2017)
  • [6] Hernandez-Hernandez J.M., Garcia-Gonzalez E.G., Brun C.E., Rudnicki M.A., The myogenic regulatory factors, determinants of muscle development, cell identity and regeneration, Semin. Cell Dev. Biol, 72, pp. 10-18, (2017)
  • [7] McPherron A.C., Lawler A.M., Lee S.J., Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member, Nature, 387, pp. 83-90, (1997)
  • [8] Benoit B., Meugnier E., Castelli M., Chanon S., Vieille-Marchiset A., Durand C., Bendridi N., Pesenti S., Monternier P.A., Durieux A.C., Et al., Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice, Nat. Med, 23, pp. 990-996, (2017)
  • [9] Thomson D.M., The Role of AMPK in the Regulation of Skeletal Muscle Size, Hypertrophy, and Regeneration, Int. J. Mol. Sci, 19, (2018)
  • [10] Kovanda A., Rezen T., Rogelj B., MicroRNA in skeletal muscle development, growth, atrophy, and disease, Wiley Interdiscip. Rev. RNA, 5, pp. 509-525, (2014)
123456