Karamitri, A., Shore, Andrew ![]() |
Abstract
Cold stress in rodents increases the expression of UCP1 and PGC-1α in brown and white adipose tissue. We have previously reported that C/EBPβ specifically binds to the CRE on the proximal Pgc-1α promoter and increases forskolin-sensitive Pgc-1α and Ucp1 expression in white 3T3-L1 preadipocytes. Here we show that in mice exposed to a cold environment for 24 h, Pgc-1α, Ucp1, and C/ebpβ but not C/ebpα or C/ebpδ expression were increased in BAT. Conversely, expression of the C/EBP dominant negative Chop10 was increased in WAT but not BAT during cold exposure. Reacclimatization of cold-exposed mice to a warm environment for 24 h completely reversed these changes in gene expression. In HIB-1B, brown preadipocytes, forskolin increased expression of Pgc-1α, Ucp1, and C/ebpβ early in differentiation and inhibited Chop10 expression. Employing chromatin immunoprecipitation, we demonstrate that C/EBPβ, CREB, ATF-2, and CHOP10 are bound to the Pgc-1α proximal CRE, but CHOP10 does not bind in HIB-1B cell lysates. Forskolin stimulation and C/EBPβ overexpression in 3T3-L1 cells increased C/EBPβ and CREB but displaced ATF-2 and CHOP10 binding to the Pgc-1α proximal CRE. Overexpression of ATF-2 and CHOP10 in 3T3-L1 cells decreased Pgc-1α transcription. Knockdown of Chop10 in 3T3-L1 cells using siRNA increased Pgc-1α transcription, whereas siRNA against C/ebpβ in HIB-1B cells decreased Pgc-1α and Ucp1 expression. We conclude that the increased cAMP stimulation of Pgc-1α expression is regulated by the combinatorial effect of transcription factors acting at the CRE on the proximal Pgc-1α promoter.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Biosciences |
Publisher: | American Society for Biochemistry and Molecular Biology |
ISSN: | 0021-9258 |
Last Modified: | 27 Oct 2022 09:24 |
URI: | https://orca.cardiff.ac.uk/id/eprint/65563 |
Citation Data
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