Interaction of SP100 with HP1 proteins: A link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment

Interaction of SP100 with HP1 proteins: A link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment

Unité de Recombinaison et Expression Génétique, Institut National de la Santé et de la Recherche Médicale U163, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15

Edited by Pierre Chambon, Institut de Génétique et de Biologie Moleculaire et Cellulaire, Strasbourg, France, and approved April 23, 1998 (received for review February 17, 1998)

Abstract

The PML/SP100 nuclear bodies (NBs) were first described as discrete subnuclear structures containing the SP100 protein. Subsequently, they were shown to contain the PML protein which is part of the oncogenic PML-RARα hybrid produced by the t(15;17) chromosomal translocation characteristic of acute promyelocytic leukemia. Yet, the physiological role of these nuclear bodies remains unknown. Here, we show that SP100 binds to members of the heterochromatin protein 1 (HP1) families of non-histone chromosomal proteins. Further, we demonstrate that a naturally occurring splice variant of SP100, here called SP100-HMG, is a member of the high mobility group-1 (HMG-1) protein family and may thus possess DNA-binding potential. Both HP1 and SP100-HMG concentrate in the PML/SP100 NBs, and overexpression of SP100 leads to enhanced accumulation of endogenous HP1 in these structures. When bound to a promoter, SP100, SP100-HMG and HP1 behave as transcriptional repressors in transfected mammalian cells. These observations present molecular evidence for an association between the PML/SP100 NBs and the chromatin nuclear compartment. They support a model in which the NBs may play a role in certain aspects of chromatin dynamics.

Footnotes

↵ * To whom reprint requests should be addressed. e-mail: adejean{at}pasteur.fr.
This paper was submitted directly (Track II) to the Proceedings Office.
Abbreviations: HP, heterochromatin protein; AD, activation domain; CD, chromo domain; CSD, chromo shadow domain; DBD, DNA-binding domain; HA, hemaglutinin; HMG, high mobility group; NB, nuclear body; CAT, chloramphenicol acetyltransferase; RA, retinoic acid; GST, glutathione S-transferase.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF056322).