TIPs are tension-responsive proteins involved in myogenic versus adipogenic differentiation.
Stretch induces lung embryonic mesenchymal cells to follow a myogenic pathway. Using this system we identified a set of stretch-responsive factors, which we referred to as TIPs (tension-induced/inhibited proteins). TIPs displayed signature motifs characteristic of nuclear receptor coregulators and chromatin remodeling enzymes. A genomic BLAST search suggested that the three TIPs identified were isoforms originated by alternative splicing from a single gene. Functional studies revealed that TIP-1 and TIP-3 were involved in the cell's selection of the myogenic or the adipogenic pathway. TIP-1, induced by stretch, promoted myogenesis, while TIP-3, inhibited by stretch, stimulated adipogenesis. The selection involved TIP-mediated chromatin remodeling via a histone acetylation process and depended on TIP-1 and TIP-3 nuclear receptor binding boxes (NRBs). This study, therefore, suggests a new developmental mechanism linking the presence or absence of tension with divergent differentiation pathways.
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Sandhya
S
Jakkaraju
Xiaoning
X
Zhe
Desi
D
Pan
Ranginee
R
Choudhury
Lucia
L
Schuger
D000123:Acetyltransferases / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly; D004622:Embryo, Mammalian / Q000166:cytology; D051548:Histone Acetyltransferases; D040542:Mechanotransduction, Cellular; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008780:Methyltransferases; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical
D002352:Carrier Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D008780:Methyltransferases; C503312:tension-induced inhibited protein, mouse; D000123:Acetyltransferases; D051548:Histone Acetyltransferases