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Molecular and Cellular Biology, April 2001, p. 2485-2495, Vol. 21, No. 7
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.7.2485-2495.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Critical Role of the HMGI(Y) Proteins in Adipocytic Cell Growth and Differentiation

Rosa Marina Melillo,1 Giovanna Maria Pierantoni,1 Stefania Scala,1 Sabrina Battista,1 Monica Fedele,1 Antonella Stella,2 Maria Cristina De Biasio,3 Gennaro Chiappetta,3 Vincenzo Fidanza,4 Gianluigi Condorelli,4 Massimo Santoro,1 Carlo M. Croce,4 Giuseppe Viglietto,3 and Alfredo Fusco2,*

Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Dipartimento di Biologiae Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli,1 and Istituto Nazionale dei Tumori Fondazione Senatore Pascale,3 80131 Naples, and Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgia di Catanzaro, Università degli Studi di Catanzaro, 88100 Catanzaro,2 Italy, and Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 191074

Received 2 June 2000/Returned for modification 31 July 2000/Accepted 11 January 2001

The high-mobility group I (HMGI) nonhistone chromosomal proteins HMGI(Y) and HMGI-C have been implicated in defining chromatin structure and in regulating the transcription of several genes. These proteins have been implicated in adipocyte homeostasis: a severe deficiency of fat tissue is found in mice with targeted disruption of the HMGI-C locus, and lipomagenesis in humans is frequently associated with somatic mutations of HMGI genes. The aim of this study was to examine the role of HMGI(Y) proteins in adipocytic cell growth and differentiation. First, we found that differentiation of the preadipocytic 3T3-L1 cell line caused early induction of HMGI(Y) gene expression. Suppression of HMGI(Y) expression by antisense technology dramatically increased the growth rate and impaired adipocytic differentiation in these cells. The process of adipogenic differentiation involves the interplay of several transcription factors, among which is the CCAAT/enhancer-binding protein (C/EBP) family of proteins. These factors are required for the transcriptional activation of adipocyte-specific genes. We also tested the hypothesis that HMGI(Y) might participate in transcriptional control of adipocyte-specific promoters. We found that HMGI(Y) proteins bind C/EBPbeta in vivo and in vitro. Furthermore, we show that HMGI(Y) strongly potentiates the capacity of C/EBPbeta to transactivate the leptin promoter, an adipose-specific promoter. Taken together, these results indicate that the HMGI(Y) proteins play a critical role in adipocytic cell growth and differentiation.

* Corresponding author. Mailing address: Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, Via Pansini, 5, 80131 Naples, Italy. Phone: 39 081 7463056. Fax: 39 081 7463037 or 7701016. E-mail: afusco{at}napoli.com.

Molecular and Cellular Biology, April 2001, p. 2485-2495, Vol. 21, No. 7
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.7.2485-2495.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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