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Molecular and Cellular Biology, September 2000, p. 6627-6637, Vol. 20, No. 18
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Involvement of Retinoblastoma Protein and HBP1 in Histone H10 Gene Expression

Claudie Lemercier, Kym Duncliffe,dagger Isabelle Boibessot, Hui Zhang, André Verdel, Dimitar Angelov,Dagger and Saadi Khochbin*

Laboratoire de Biologie Moléculaire et Cellulaire de la Différentiation---INSERM U309, Equipe, Chromatine et Expression des Gènes, Institut Albert Bonniot, Faculté de Médecine, Domaine de la Merci, 38706 La Tronche Cedex, France

Received 28 March 2000/Returned for modification 17 May 2000/Accepted 8 June 2000

The histone H10-encoding gene is expressed in vertebrates in differentiating cells during the arrest of proliferation. In the H10 promoter, a specific regulatory element, which we named the H4 box, exhibits features which implicate a role in mediating H10 gene expression in response to both differentiation and cell cycle control signals. For instance, within the linker histone gene family, the H4 box is found only in the promoters of differentiation-associated subtypes, suggesting that it is specifically involved in differentiation-dependent expression of these genes. In addition, an element nearly identical to the H4 box is conserved in the promoters of histone H4-encoding genes and is known to be involved in their cell cycle-dependent expression. The transcription factors interacting with the H10 H4 box were therefore expected to link differentiation-dependent expression of H10 to the cell cycle control machinery. The aim of this work was to identify such transcription factors and to obtain information concerning the regulatory pathway involved. Interestingly, our cloning strategy led to the isolation of a retinoblastoma protein (RB) partner known as HBP1. HBP1, a high-mobility group box transcription factor, interacted specifically with the H10 H4 box and moreover was expressed in a differentiation-dependent manner. We also showed that the HBP1-encoding gene is able to produce different forms of HBP1. Finally, we demonstrated that both HBP1 and RB were involved in the activation of H10 gene expression. We therefore propose that HBP1 mediates a link between the cell cycle control machinery and cell differentiation signals. Through modulating the expression of specific chromatin-associated proteins such as histone H10, HBP1 plays a vital role in chromatin remodeling events during the arrest of cell proliferation in differentiating cells.

* Corresponding author. Mailing address: Laboratoire de Biologie Moléculaire et Cellulaire de la Différentiation---INSERM U309, Equipe, chromatine et expression des gènes, Institut Albert Bonniot, Faculté de Médecine, Domaine de la Merci, 38706 La Tronche Cedex, France. Phone: (33) 4 76 54 95 83. Fax: (33) 4 76 54 95 95. E-mail: khochbin{at}ujf-grenoble.fr.

dagger Present address: Department of Clinical Pharmacology, Flinders Medical Centre, Bedford Park, South Australia 5042, Australia.

Dagger Present address: Institut of Solid State Physics, Bulgarian Academy of Science, 1784 Sofia, Bulgaria.

Molecular and Cellular Biology, September 2000, p. 6627-6637, Vol. 20, No. 18
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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