Table 1.
Human GFAP Promoter Regions.
| gfa2 Regions | |||
|---|---|---|---|
| Region | Locationa | Transcription factor sites | Effect on transgene activity |
| Upstream | −2162 to −1757 | an alu sequence spans -2069 to −1757 | No effect |
| A | −1756 to −1612 | NFI | Not tested |
| B | −1611 to −1488 | See subregions below | Required |
| B1 | −1611 to −1581 | consensus AP−1, NFI | Mutation in ABC1D reduces activity >99% |
| B2 | −1580 to −1548 | AP−1, NFI, Sp1 | Mutation in ABC1D reduces activity ∼84% and contributes to spatial distribution, and suppression in neurons |
| B3 | −1547 to −1519 | Sp1 (x2) | Mutation in ABC1D reduces activity ∼87% and delays developmental onset |
| B4 | −1518 to −1488 | STAT3 | Mutation in ABC1D reduces activity ∼58% and delays developmental onset. Also contributes to spatial distribution and suppression in neurons |
| C | −1487 to −133 | See subregions below | |
| C1 | −1487 to −1255 | CSL, GATA, NF-κB (see C1.1 and C1.2 subregions below) | Required for general expression throughout the CNS |
| C1.1 | −1487 to −1433 | GATA | Contributes to general CNS expression |
| C1.2 | −1442 to −1398 | NF-κB | Contributes to silencing neuronal GFAP expression |
| C2 | −1279 to −1025 | CSL, RBPJ | Strongly represses activity |
| C3 | −1049 to −796 | Contributes to general CNS expression and silencing expression in neurons | |
| C4 | −820 to −567 | RBPJ, CSL, Nkx2.1 | Little if any effect |
| C5 | −591 to −339 | RAR | Little if any effect |
| C6 | −363 to −132 | AP−1, CSL, DRE | Little if any effect |
| D | −132 to −57 | DRE, NFI (x2) | No effect (but see text for caveats) |
| BP | −56 to +47 | Not tested | |
|
hGFAP Transgene Promotersb | |||
| Name | GenBank coordinates | Expression characteristics | |
| gfa2 | −2162 to +47 | Similar to endogenous GFAP except weak response to injury | |
| ABCD | −1756 to +47 | Similar to gfa2 | |
| ABC1D | −1756 to −1255/−132 to +47 | Similar to gfa2 | |
| ABD | −1756 to −1488/−132 to +47 | Expression in astrocytes largely limited to the dorsal and caudal cortical regions, hippocampus, and caudal vermis of the cerebellum; expresses in several populations of neurons | |
aLocations are relative to the RNA start site, using NCBI Reference Sequence NC_000017.11.bThe basal promoter (BP) is present in each of these promoters, and has the protein initiating ATG at +15 changed to TTG.