A new role for sterol regulatory element binding protein 1 transcription factors in the regulation of muscle mass and muscle cell differentiation.
The role of the transcription factors sterol regulatory element binding protein 1a (SREBP-1a) and SREBP-1c in the regulation of cholesterol and fatty acid metabolism has been well studied; however, little is known about their specific function in muscle. In the present study, analysis of recent microarray data from muscle cells overexpressing SREBP1 suggested that they may play a role in the regulation of myogenesis. We then demonstrated that SREBP-1a and -1c inhibit myoblast-to-myotube differentiation and also induce in vivo and in vitro muscle atrophy. Furthermore, we have identified the transcriptional repressors BHLHB2 and BHLHB3 as mediators of these effects of SREBP-1a and -1c in muscle. Both repressors are SREBP-1 target genes, and they affect the expression of numerous genes involved in the myogenic program. Our findings identify a new role for SREBP-1 transcription factors in muscle, thus linking the control of muscle mass to metabolic pathways.
Lecomte
Virginie
V
INSERM, U870, F-69921 Oullins Cedex, France.
Meugnier
Emmanuelle
E
Euthine
Vanessa
V
Durand
Christine
C
Freyssenet
Damien
D
Nemoz
Georges
G
Rome
Sophie
S
Vidal
Hubert
H
Lefai
Etienne
E
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D015536:Down-Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D024510:Muscle Development / Q000235:genetics / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism*; D009133:Muscular Atrophy / Q000209:etiology; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D051780:Sterol Regulatory Element Binding Protein 1; C107989:BHLHE40 protein, human; C422085:BHLHE41 protein, human; C497387:SREBF1 protein, human