CARM1 promotes adipocyte differentiation by coactivating PPARgamma.
The coactivator-associated arginine methyltransferase 1 (CARM1) is recruited to gene promoters by many transcription factors. To identify new pathways that use CARM1, we carried out a comprehensive transcriptome analysis of CARM1-knockout embryos. By using complementary DNA microarrays and serial analysis of gene expression, we identified various genes involved in lipid metabolism that were underrepresented in CARM1-knockout embryos, indicating an important role for this coactivator in adipose tissue biology. We also observed that the amount of brown fat in CARM1-knockout embryos is reduced. Furthermore, cells lacking CARM1 have a severely curtailed potential to differentiate into mature adipocytes. Reporter experiments and chromatin immunoprecipitation analysis show that CARM1 regulates these processes by acting as a coactivator for peroxisome proliferator-activated receptor gamma (PPARgamma). Together, these results show that CARM1 promotes adipocyte differentiation by coactivating PPARgamma-mediated transcription and thus might be important in energy balance.
Yadav
Neelu
N
Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park, Smithville, Texas 78957, USA.
Cheng
Donghang
D
Richard
Stephane
S
Morel
Melanie
M
Iyer
Vishwanath R
VR
Aldaz
C Marcelo
CM
Bedford
Mark T
MT
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000201:enzymology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects / Q000201:enzymology; D004967:Estrogens / Q000494:pharmacology; D020869:Gene Expression Profiling; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D004967:Estrogens; D047495:PPAR gamma; D012333:RNA, Messenger; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1