The Centromeric/Nucleolar Chromatin Protein ZFP-37 May Function to Specify Neuronal Nuclear Domains

doi:10.1074/jbc.273.15.9099

The Centromeric/Nucleolar Chromatin Protein ZFP-37 May Function to Specify Neuronal Nuclear Domains*

From the ^‡Department of Cell Biology and Genetics and the ^‡Department of Anatomy, Erasmus University, P. O. Box 1738, 3000 DR Rotterdam, The Netherlands, the ^**Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, and ^‖Children’s Hospital, University of Mainz, D-55101 Mainz, Germany

Abstract

Murine ZFP-37 is a member of the large family of C₂H₂ type zinc finger proteins. It is characterized by a truncated NH₂-terminal Krüppel-associated box and is thought to play a role in transcriptional regulation. During development Zfp-37mRNA is most abundant in the developing central nervous system, and in the adult mouse expression is restricted largely to testis and brain. Here we show that at the protein level ZFP-37 is detected readily in neurons of the adult central nervous system but hardly in testis. In brain ZFP-37 is associated with nucleoli and appears to contact heterochromatin. Mouse and human ZFP-37 have a basic histone H1-like linker domain, located between KRAB and zinc finger regions, which binds double-stranded DNA. Thus we suggest that ZFP-37 is a structural protein of the neuronal nucleus which plays a role in the maintenance of specialized chromatin domains.

Footnotes

↵* This work was supported in part by the Medical Research Council (United Kingdom) and the Erasmus University, Rotterdam (The Netherlands).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵§ Supported by a Human Frontiers of Science and a European Economic Community human capital mobility fellowship. Present address: Laboratoire Expérimental de Thérapie Génique, Centre Hayem, Hôpital Saint-Louis, 1 Av. C. Vellefaux, 75010 Paris, France.
↵¶ Supported by a Medical Research Council Ph.D. fellowship.
↵§§ Supported by a fellowship from the Dutch Royal Academy of Arts and Sciences.
↵¶¶ Supported by long term fellowships from the European Molecular Biology Organization and the Dutch Royal Academy of Arts and Sciences. To whom correspondence should be addressed. Tel.:31-10-408-7169; Fax: 31-10-436-0225; E-mail:galjart{at}ch1.fgg.eur.nl.
↵1 The abbreviations used are: KRAB, Krüppel-associated box; ZFP, zinc finger protein; GST, glutathione S-transferase; PCR, polymerase chain reaction; bp, base pair(s); GFP, green fluorescent protein; BFP, blue fluorescent protein; NoLS, nucleolus-localizing sequence; FITC, fluorescein isothiocyanate; DAPI, 4′,6-diamidino-2-phenylindole; DABCO, 1,4-diazabicyclo-[2,2,2]octane.
↵2 S. Dreyer, A. Winterpacht, and B. Lee, unpublished results.
↵3 D. Michalovich, T. Verkerk, F. Grosveld, and N. Galjart, unpublished observations.
- Received December 17, 1997.
- Revision received February 4, 1998.
The American Society for Biochemistry and Molecular Biology, Inc.