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GFAP promoter elements required for region‐specific and astrocyte‐specific expression

Lee, Youngjin, Messing, Albee, Su, Mu, Brenner, Michael·2008·Glia
DOI 10.1002/glia.20622
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Abstract

Glial fibrillary acidic protein (GFAP) is the major intermediate filament protein in astrocytes, one of the most abundant cell types in the vertebrate central nervous system (CNS). Transcriptional regulation of GFAP is of interest because of its astrocyte‐specificity and its upregulation during development and CNS injury. A 2.2 kb human GFAP promoter, gfa2, has been found to express in astrocytes throughout the CNS. In contrast, we recently found that the 448 bp gfa28 promoter expresses in only restricted CNS regions, and is active in neurons as well as astrocytes. In the present study we have used transgenic mice to investigate which DNA regions deleted from gfa2 in the formation of gfa28 are responsible for these differences. We have found that a 55 bp segment spanning bp −1488 to −1434 with respect to the RNA start site contains region‐specific elements and that a 45 bp sequence spanning bp −1443 to −1399 is required for silencing expression in neurons. These data also further confirm the heterogeneity of astrocytes and neurons in the activation and repression of the GFAP gene, respectively. These studies also generated a novel 681 bp GFAP promoter, gfaABC 1 D, that has essentially the same expression pattern as the 2210 bp gfa2 promoter, and about twofold greater activity, recommending it for gene targeting applications in which size matters. In addition, a 681 bp gfaABC 1(mC 1.1)D variant was generated that could limit expression of transgenes to astrocytes in the dorsal and caudal cortex, hippocampus and caudal vermis of the cerebellum. © 2008 Wiley‐Liss, Inc.

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  • Neuronal dysfunction of striatal neurons precedes their degeneration, and the dopamine receptor D2 (DRD2) MSNs of the indirect pathway are the first affected in HD models and patients.

    “Neuronal dysfunction of striatal neurons precedes their degeneration, and the dopamine receptor D2 (DRD2) MSNs of the indirect pathway are the first affected in HD models and patients 33,34,35,36 .”

    From SREBP2 gene therapy targeting striatal astrocytes ameliorates Huntington’s disease phenotypes (2021) · cites this paper as [36]

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Research works printed but not linked: 36

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Metadata

Authors
Lee, Y., Messing, A., Su, M., & Brenner, M.
Venue
Glia
Publisher
Wiley
Published
2008-01-31
Volume
56
Issue
5
Pages
481-493
ISSN
  • 0894-1491
  • 1098-1136
DOI
10.1002/glia.20622
Cited by
424
References
1
Language
en
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)

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