A novel polymorphic AP-1 binding element of the GFAP promoter is associated with different allelic transcriptional activities.

[alexander disease]

The Glial Fibrillary Acidic Protein (GFAP ) gene encodes a cytoskeletal protein belonging to the intermediate filament family whose expression is considered as a marker of astrocytes differentiation . GFAP expression , shown to be upregulated as a consequence of brain gliosis , depends on hormones , growth factors , cytokine , and transcription factors and , among these latters , activator protein 1 (AP -1 ) has been demonstrated to play a crucial role . In this study , we have focused on a 2 .2 kb sequence of the regulatory region located upstream of the GFAP gene , searching in a panel of control individuals for single -nucleotide polymorphisms (SNPs ) that could modulate GFAP transcription . Among four SNPs of the GFAP promoter whose alleles have been predicted by in silico analysis to induce differences in the pattern of binding transcription factors , we have identified a new AP -1 binding site lying at -250 bp upstream from the GFAP transcriptional start site . The two alleles of this polymorphic locus have shown to bind the AP -1 complex to different extents , thus promoting variable transcriptional activities of the GFAP promoter . Therefore , these SNP alleles may , among others , mediate the effects of GFAP mutations , thus explaining the phenotypic heterogeneity of Alexander disease .

Diseases
Validation

Diseases presenting "brain gliosis" symptom

alexander disease

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