TY - JOUR
T1 - Early adipogenesis is regulated through USP7-mediated deubiquitination of the histone acetyltransferase TIP60
AU - Gao, Yuan
AU - Koppen, Arjen
AU - Rakhshandehroo, Maryam
AU - Tasdelen, Ismayil
AU - Van De Graaf, Stan F.
AU - Van Loosdregt, Jorg
AU - Van Beekum, Olivier
AU - Hamers, Nicole
AU - Van Leenen, Dik
AU - Berkers, Celia R.
AU - Berger, Ruud
AU - Holstege, Frank C.P.
AU - Coffer, Paul J.
AU - Brenkman, Arjan B.
AU - Ovaa, Huib
AU - Kalkhoven, Eric
N1 - Funding Information:
We thank M.M. Maurice, J. Bartek, J. Lukas and D. Trouche for various plasmid constructs, A. Veenstra, M.J. Groot Koerkamp, J. Pronk and M. Vromans for technical assistance, M. Boekschoten for his help with Ingenuity Pathway analysis, and S. Lens, G. Kops and T. Dansen for their helpful discussions. This study was supported by the research programme of The Netherlands Metabolomics Centre, which is part of The Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO).
PY - 2013
Y1 - 2013
N2 - Transcriptional coregulators, including the acetyltransferase Tip60, have a key role in complex cellular processes such as differentiation. Whereas post-translational modifications have emerged as an important mechanism to regulate transcriptional coregulator activity, the identification of the corresponding demodifying enzymes has remained elusive. Here we show that the expression of the Tip60 protein, which is essential for adipocyte differentiation, is regulated through polyubiquitination on multiple residues. USP7, a dominant deubiquitinating enzyme in 3T3-L1 adipocytes and mouse adipose tissue, deubiquitinates Tip60 both in intact cells and in vitro and increases Tip60 protein levels. Furthermore, inhibition of USP7 expression and activity decreases adipogenesis. Transcriptome analysis reveals several cell cycle genes to be co-regulated by both Tip60 and USP7. Knockdown of either factor results in impaired mitotic clonal expansion, an early step in adipogenesis. These results reveal deubiquitination of a transcriptional coregulator to be a key mechanism in the regulation of early adipogenesis.
AB - Transcriptional coregulators, including the acetyltransferase Tip60, have a key role in complex cellular processes such as differentiation. Whereas post-translational modifications have emerged as an important mechanism to regulate transcriptional coregulator activity, the identification of the corresponding demodifying enzymes has remained elusive. Here we show that the expression of the Tip60 protein, which is essential for adipocyte differentiation, is regulated through polyubiquitination on multiple residues. USP7, a dominant deubiquitinating enzyme in 3T3-L1 adipocytes and mouse adipose tissue, deubiquitinates Tip60 both in intact cells and in vitro and increases Tip60 protein levels. Furthermore, inhibition of USP7 expression and activity decreases adipogenesis. Transcriptome analysis reveals several cell cycle genes to be co-regulated by both Tip60 and USP7. Knockdown of either factor results in impaired mitotic clonal expansion, an early step in adipogenesis. These results reveal deubiquitination of a transcriptional coregulator to be a key mechanism in the regulation of early adipogenesis.
UR - https://www.scopus.com/pages/publications/84886867084
U2 - 10.1038/ncomms3656
DO - 10.1038/ncomms3656
M3 - Article
C2 - 24141283
AN - SCOPUS:84886867084
SN - 2041-1723
VL - 4
JO - Nature communications
JF - Nature communications
M1 - 2656
ER -