Ms. Jiang et Md. Lane, Sequential repression and activation of the CCAAT enhancer-binding protein-alpha (C/EBP alpha) gene during adipogenesis, P NAS US, 97(23), 2000, pp. 12519-12523
Citations number
24
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
CCAAT enhancer-binding protein-alpha (C/EBP alpha) functions as a pleiotrop
ic transcriptional activator of adipocyte genes during adipogenesis. Nuclea
r factor C/EBP undifferentiated protein (CUP), an isoform of activator prot
ein-2 alpha (AP-2 alpha), binds to repressive elements in the C/EBP alpha g
ene promoter, silencing the gene until late in the differentiation program.
The CUP regulatory element overlaps a Sp (GT-box) element in the promoter
to which Sp3 (or Sp1) can bind. Binding by sp3 or Sp1 and CUP/AP2-alpha is
mutually exclusive. Sp3 is a strong transcriptional activator of the C/EBP
alpha gene promoter in 3T3-L1 preadipocytes and Schneider cells, this activ
ation being repressed by CUP/AP-2 alpha. Sp3 is expressed throughout differ
entiation, whereas CUP/AP-2 alpha. which is expressed only by preadipocytes
. is down-regulated during differentiation coincident with transcription of
the C/EBP alpha gene. Thus. CUP/AP-2 alpha delays access of Sp3 to the Sp
regulatory element. preventing premature expression of C/EBP alpha and ther
eby interference by C/EBP alpha (which is antimitotic) with mitotic clonal
expansion, an essential early event in the differentiation program.