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Molecular and Cellular Biology, April 2001, p. 2485-2495, Vol. 21, No. 7
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/EBP
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
in vivo and in vitro. Furthermore, we show that HMGI(Y)
strongly potentiates the capacity of C/EBP
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.
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