Adjacent nuclear factor-1 and activator protein binding sites in the enhancer of the neurotropic JC virus. A common characteristic of many brain-specific genes.

K Amemiya,R Traub,L Durham,E.O Major

doi:10.1016/s0021-9258(19)49698-1

Abstract

JC virus is a neurotropic virus that causes the demyelinating disease progressive multifocal leukoencephalopathy in humans. In order to understand the neurotropic nature of this virus, we examined the binding of nuclear proteins to the viral regulatory region. A close association of nuclear factor-1 (NF-1) and Jun protein binding sites was found. These binding sites were either adjacent or overlapped each other. Depending on the order of binding, there was some interference of binding of the NF-1 protein by Jun even at a non-Jun binding site. This suggests that there may be a direct interaction between these proteins. Examination of the regulatory region of a number of genes expressed in the central and peripheral nervous systems revealed that many of these genes apparently have adjacent NF-1 and activator protein binding sites immediately upstream from the mRNA start site. Since it had been demonstrated that nuclear proteins from brain and non-brain cells could interact with these sites, it is probable that the NF-1- and Jun-related proteins which interact at these sites are involved in the basal activity of these genes. It appears that adjacent binding sites for NF-1 and Jun immediately upstream from the mRNA start site may be a characteristic of many genes expressed in the nervous system.

Highlights

From the Molecular Virology and Genetics Section, LaboratoofryViral and Molecular Pathogenesis, National Instituotef Neurological Disorders and Stroke, National Institutoef Health, Bethesda, Maryland20892 and SIgen, Inc., Rockuille, Maryland 20852
JC virus (JCV),’ which is a human polyomavirus, has a relatively restricted host range (Padgett et al, 1977).It is the etiological agent of the human demyelinating disease, progressive multifocal leukoencephalopathy
Since it had been demonstrated that nuclear proteins shown that one restriction to thehost range of JCV is at the frombrainandnon-brain cells couldinteract with level of transcription (Kenney et al, 1984)

Summary

THEJOURNALOF BIOLOGICAL CHEMISTRY

Vol 267, No., Issue of July 15, pp. 14204-14211, 1992 Printed in U.S.A. From the Molecular Virology and Genetics Section, LaboratoofryViral and Molecular Pathogenesis, National Instituotef Neurological Disorders and Stroke, National Institutoef Health, Bethesda, Maryland20892 and SIgen, Inc., Rockuille, Maryland 20852. Since it had been demonstrated that nuclear proteins shown that one restriction to thehost range of JCV is at the frombrainandnon-brain cells couldinteract with level of transcription (Kenney et al, 1984) The regulatory these sites, it is probablethatthe NF-1- andJun- region of JCV consistsof two direct 98-bp repeat units (Frisrelated proteins which interact at these sites are in- que et al, 1984). Unlike other primate polyomaviruses like volved in the basal activity of these genes It appears SV40 and BK virus, each repeat unit of the prototype virus, that adjacent bindingsites for NF-1 and Jun immedi- Madl, contains a T/A-rich region which presumably serves ately upstreamfromthemRNA start site maybe a as theTATA box. The basal transcriptional activity would require the involve- In several regions of the JCV promoter-enhancer region, ment of another set of proteins which may recognize specific we have found a close association of nuclear factor-1 (NF-1). Bp HindIII-ApaI fragment which contained part of the regulatory region of the mouse MBP gene came from the plasmid pJCC138

RESULTS

DISCUSSION

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