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Analysis of a Segment of the Human Glial Fibrillary Acidic Protein Gene That Directs Astrocyte‐Specific Transcription
Author(s) -
Masood Khalid,
Besnard François,
Su Yuan,
Brenner Michael
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03551.x
Subject(s) - glial fibrillary acidic protein , biology , astrocyte , gfap stain , microbiology and biotechnology , transcription factor , gene , reporter gene , transcription (linguistics) , gene expression , genetics , linguistics , immunohistochemistry , philosophy , neuroscience , immunology , central nervous system
To understand astrocyte‐specific transcription, we have been studying the human gfa gene. This gene encodes glial fibrillary acidic protein (GFAP), an intermediate filament protein expressed primarily in astrocytes. A survey of the gfa 5′ flanking region showed it to contain several segments that contribute to expression of a chloramphenicol acetyltransferase reporter gene in transfected cells. The most active of these was the 124‐bp B region, which spans bp ‐1612 to ‐1489. We have now used site‐ directed mutagenesis to analyze this region in greater detail, and show that the B region itself contains several important elements. The most crucial of these is a consensus AP‐1 sequence, the binding site for the Fos and Sun families of transcription factors. The presence of members of both these families in the glial fibrillary acidic protein‐ expressing U251 cell line used for our transfection studies was verified by gel mobility‐shift experiments. This is the first demonstration of the functioning of a specific transcription factor site for astrocytes, and provides a focus for future studies of glial fibrillary acidic protein regulation during development and reactive gliosis.