TY - JOUR
T1 - SIRT1 controls the transcription of the peroxisome proliferator-activated receptor-γ co-activator-1α(PGC-1α) gene in skeletal muscle through the PGC-1α autoregulatory loop and interaction with MyoD
AU - Amat, Ramon
AU - Planavila, Anna
AU - Chen, Shen Liang
AU - Iglesias, Roser
AU - Giralt, Marta
AU - Villarroya, Francesc
PY - 2009/8/14
Y1 - 2009/8/14
N2 - Peroxisome proliferator activated receptor-γ co-activator-1a (PGC-1α) is a transcriptional co-activator that coordinately regulates the expression of distinct sets of metabolism-related genes in different tissues. Here we show that PGC-1α expression is reduced in skeletal muscles from mice lacking the sirtuin family deacetylase SIRT1. Conversely, SIRT1 activation or overexpression in differentiated C2C12 myotubes increased PGC-1α mRNA expression. The transcription-promoting effects of SIRT1 occurred through stimulation of PGC-1b promoter activity and were enhanced by co-transfection of myogenic factors, such as myocyte enhancer factor 2 (MEF2) and, especially, myogenic determining factor (MyoD). SIRT1 bound to the proximal promoter region of the PGC-1α gene, an interaction potentiated by MEF2C or MyoD, which also interact with this region. In the presence of MyoD, SIRT1 promoted a positive autoregulatory PGC-1α expression loop, such that overexpression of PGC-1α increased PGC-1α promoter activity in the presence of co-expressed MyoD and SIRT1. Chromatin immunoprecipitation showed that SIRT1 interacts with PGC-1α promoter and increases PGC-1b recruitment to its own promoter region. Immunoprecipitation assays further showed that SIRT1- PGC-1α interactions are enhanced by MyoD. Collectively, these data indicate that SIRT1 controls PGC-1α gene expression in skeletal muscle and that MyoD is a key mediator of this action. The involvement of MyoDin SIRT1-dependent PGC-1α expression may help to explain the ability of SIRT1 to drive muscle-specific gene expression and metabolism. Autoregulatory control of PGC-1α gene transcription seems to be a pivotal mechanism for conferring a transcription-activating response to SIRT1 in skeletal muscle.
AB - Peroxisome proliferator activated receptor-γ co-activator-1a (PGC-1α) is a transcriptional co-activator that coordinately regulates the expression of distinct sets of metabolism-related genes in different tissues. Here we show that PGC-1α expression is reduced in skeletal muscles from mice lacking the sirtuin family deacetylase SIRT1. Conversely, SIRT1 activation or overexpression in differentiated C2C12 myotubes increased PGC-1α mRNA expression. The transcription-promoting effects of SIRT1 occurred through stimulation of PGC-1b promoter activity and were enhanced by co-transfection of myogenic factors, such as myocyte enhancer factor 2 (MEF2) and, especially, myogenic determining factor (MyoD). SIRT1 bound to the proximal promoter region of the PGC-1α gene, an interaction potentiated by MEF2C or MyoD, which also interact with this region. In the presence of MyoD, SIRT1 promoted a positive autoregulatory PGC-1α expression loop, such that overexpression of PGC-1α increased PGC-1α promoter activity in the presence of co-expressed MyoD and SIRT1. Chromatin immunoprecipitation showed that SIRT1 interacts with PGC-1α promoter and increases PGC-1b recruitment to its own promoter region. Immunoprecipitation assays further showed that SIRT1- PGC-1α interactions are enhanced by MyoD. Collectively, these data indicate that SIRT1 controls PGC-1α gene expression in skeletal muscle and that MyoD is a key mediator of this action. The involvement of MyoDin SIRT1-dependent PGC-1α expression may help to explain the ability of SIRT1 to drive muscle-specific gene expression and metabolism. Autoregulatory control of PGC-1α gene transcription seems to be a pivotal mechanism for conferring a transcription-activating response to SIRT1 in skeletal muscle.
UR - http://www.scopus.com/inward/record.url?scp=69249116960&partnerID=8YFLogxK
U2 - 10.1074/jbc.M109.022749
DO - 10.1074/jbc.M109.022749
M3 - 期刊論文
C2 - 19553684
AN - SCOPUS:69249116960
SN - 0021-9258
VL - 284
SP - 21872
EP - 21880
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 33
ER -