HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 25, 17180-17188, June 23, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/25/17180    most recent M601295200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Musri, M. M. Articles by Párrizas, M. Search for Related Content PubMed PubMed Citation Articles by Musri, M. M. Articles by Párrizas, M. Social Bookmarking                      What's this?

Histone H3 Lysine 4 Dimethylation Signals the Transcriptional Competence of the Adiponectin Promoter in Preadipocytes^*

Melina M. Musri, Helena Corominola, Roser Casamitjana, Ramon Gomis¹, and Marcelina Párrizas¹²

From the Endocrinology and Nutrition Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer Hospital Clínic, Universitat de Barcelona, 08036 Barcelona, Spain and Biochemistry and Molecular Genetics Department, Hospital Clínic, 08036 Barcelona, Spain

Adipogenesis is regulated by a coordinated cascade of sequence-specific transcription factors and coregulators with chromatin-modifying activities that are between them responsible for the establishment of the gene expression pattern of mature adipocytes. Here we examine the histone H3 post-translational modifications occurring at the promoters of key adipogenic genes during adipocyte differentiation. We show that the promoters of apM1, glut4, gpd1, and leptin are enriched in dimethylated histone H3 Lys⁴ (H3-K4) in 3T3-L1 fibroblasts, where none of these genes are yet expressed. A detailed study of the apM1 locus shows that H3-K4 dimethylation is restricted to the promoter region in undifferentiated cells and associates with RNA polymerase II (pol II) loading. The beginning of apM1 transcription at the early stages of adipogenesis coincides with promoter H3 hyperacetylation and H3-K4 trimethylation. At the coding region, H3 acetylation and dimethylation, as well as pol II binding, are found in cells at later stages of differentiation, when apM1 transcription reaches its maximal peak. This same pattern of histone modifications is detected in mouse primary preadipocytes and adipocytes but not in a related fibroblast cell line that is not committed to an adipocyte fate. Inhibition of H3-K4 methylation by treatment of 3T3-L1 cells with methylthioadenosine results in decreased apM1 gene expression as well as decreased adipogenesis. Taken together, our data indicate that H3-K4 dimethylation and pol II binding to the promoter of key adipogenic genes are distinguishing marks of cells that have undergone determination to a preadipocyte stage.

Received for publication, February 9, 2006 , and in revised form, March 27, 2006.

^* This work was supported by Ministerio de Ciencia y Tecnología (Spain) Grant SAF2003-06018. The research group was supported by Ministerio de Sanidad y Consumo (Spain) Grants Redes CO3/08 and G03/212 and Generalitat de Catalunya Grant SGR-2005. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table 1 and Fig. 1.

¹ These authors contributed equally to this work.

² Recipient of a Ramón y Cajal contract from the Ministerio de Educación y Ciencia (Spain). To whom correspondence should be addressed: Hospital Clínic, Villarroel 170, Esc. 9, Pl. 5, Barcelona 08036, Spain. E-mail: mparrizas{at}ambtu.bcn.es.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Laumen, A. D. Saningong, I. M. Heid, J. Hess, C. Herder, M. Claussnitzer, J. Baumert, C. Lamina, W. Rathmann, E.-M. Sedlmeier, et al. Functional Characterization of Promoter Variants of the Adiponectin Gene Complemented by Epidemiological Data Diabetes, April 1, 2009; 58(4): 984 - 991. [Abstract] [Full Text] [PDF]

				G. Li, C. M. Weyand, and J. J. Goronzy Epigenetic mechanisms of age-dependent KIR2DL4 expression in T cells J. Leukoc. Biol., September 1, 2008; 84(3): 824 - 834. [Abstract] [Full Text] [PDF]

				S. Karahuseyinoglu, C. Kocaefe, D. Balci, E. Erdemli, and A. Can Functional Structure of Adipocytes Differentiated from Human Umbilical Cord Stroma-Derived Stem Cells Stem Cells, March 1, 2008; 26(3): 682 - 691. [Abstract] [Full Text] [PDF]

				A. Glasow, A. Barrett, K. Petrie, R. Gupta, M. Boix-Chornet, D.-C. Zhou, D. Grimwade, R. Gallagher, M. von Lindern, S. Waxman, et al. DNA methylation-independent loss of RARA gene expression in acute myeloid leukemia Blood, February 15, 2008; 111(4): 2374 - 2377. [Abstract] [Full Text] [PDF]

				F. A. Myers, P. Lefevre, E. Mantouvalou, K. Bruce, C. Lacroix, C. Bonifer, A. W. Thorne, and C. Crane-Robinson Developmental activation of the lysozyme gene in chicken macrophage cells is linked to core histone acetylation at its enhancer elements Nucleic Acids Res., September 1, 2006; 34(14): 4025 - 4035. [Abstract] [Full Text] [PDF]