Analysis of the human MBP promoter in primary cultures of oligodendrocytes : positive and negative cis-acting elements in the proximal MBP promoter mediate oligodendrocyte-specific expression of MBP

L WRABETZ; S SHUMAS; J GRINSPAN; M. L FELDRI; D BOZYCZKO; F. A MCMORRIS; D PLEASURE; J KAMHOLZ

doi:10.1002/jnr.490360412

Back

Analysis of the human MBP promoter in primary cultures of oligodendrocytes : positive and negative cis-acting elements in the proximal MBP promoter mediate oligodendrocyte-specific expression of MBP

Journal article

Peer reviewed

Analysis of the human MBP promoter in primary cultures of oligodendrocytes : positive and negative cis-acting elements in the proximal MBP promoter mediate oligodendrocyte-specific expression of MBP

L WRABETZ, S SHUMAS, J GRINSPAN, M. L FELDRI, D BOZYCZKO, F. A MCMORRIS, D PLEASURE and J KAMHOLZ

Journal of neuroscience research, Vol.36(4), pp.455-471

1993

DOI: 10.1002/jnr.490360412

PMID: 7505842

View Online

Abstract

Since the regulation of myelin basic protein expression depends primarily on the initiation of transcription, we analyzed the 5' flanking region of the human myelin basic protein gene in transient transfection studies in primary cultures of developing oligodendrocytes. We demonstrated that 149 base pairs 5' of the initiation of transcription was sufficient to direct oligodendrocyte-specific expression of myelin basic protein. The capsite of the fusion transcript was identical with that of the endogenous myelin basic protein transcript, and chloramphenicol acetyl transferase reporter gene expression was restricted to oligodendrocytes in these cultures. Within this 149 base pair region, one distal, negative cis-acting segment, containing a consensus nuclear factor I site, and one proximal, positive cis-acting segment were identified. The distal segment behaved more negatively in Cos-7 cells than in oligodendrocytes, reducing expression to background levels. Furthermore, these functionally important cis-acting segments bound oligodendrocyte nuclear proteins in a pattern differing from other cells, including Cos-7 cells. Interestingly, the distal segment increased heterologous SV40 promoter activity in oligodendrocytes but had no effect on the SV40 promoter in Cos-7 cells. We conclude that the functionally negative distal segment may mediate oligodendrocyte-specific expression of MBP by restricting its expression in other cells. These experiments strongly support using primary cultures of oligodendrocytes for analyzing the myelin-specific promoters.

Fundamental and applied biological sciences. Psychology

Vertebrates: nervous system and sense organs

Biological and medical sciences

Isolated neuron and nerve. Neuroglia

Details

Title: Subtitle: Analysis of the human MBP promoter in primary cultures of oligodendrocytes : positive and negative cis-acting elements in the proximal MBP promoter mediate oligodendrocyte-specific expression of MBP
Creators: L WRABETZ - Univ. Pennsylvania school medicine, dep. neurology, United States
S SHUMAS - Univ. Pennsylvania school medicine, dep. neurology, United States
J GRINSPAN - Univ. Pennsylvania school medicine, dep. neurology, United States
M. L FELDRI - Univ. Pennsylvania school medicine, dep. neurology, United States
D BOZYCZKO - Univ. Pennsylvania school medicine, dep. neurology, United States
F. A MCMORRIS - Univ. Pennsylvania school medicine, dep. neurology, United States
D PLEASURE - Univ. Pennsylvania school medicine, dep. neurology, United States
J KAMHOLZ - Univ. Pennsylvania school medicine, dep. neurology, United States
Resource Type: Journal article
Publication Details: Journal of neuroscience research, Vol.36(4), pp.455-471
Publisher: Wiley-Liss; New York, NY
DOI: 10.1002/jnr.490360412
PMID: 7505842
ISSN: 0360-4012
eISSN: 1097-4547
Language: English
Date published: 1993
Academic Unit: Neurology; Psychiatry
Record Identifier: 9984020773002771

Metrics

23 Record Views

20 Times Cited - Web of Science

See more details