Filaments intermédiaires et expression génétique neuronale

Abstract

In the developing nervous system, intermediate filaments have a specific and diversified pattern of expression. In particular, peripherin is expressed only in neurons and mostly in the peripheral nervous system where its expression is associated with terminal differentiation. Molecular analysis of the promoter of the peripherin gene revealed that the 98 base pairs preceding the transcription start site were sufficient to confer cell-type-specific expression. Three regulatory sequence elements named PER1, PER2 and PER3 were found in this region. Experiments designed to test the contribution of each element to the regulation of peripherin gene transcription showed that PER2 and PER3 were important in determining the level of expression, while PER1 was important for cell-type specificity. The PER1 element is also particular in that it overlaps the TATA box and interacts with a DNA-binding protein found in peripherin expressing cell lines. These observations indicate that cooperative interactions between different regions of the promoter are necessary for efficient and cell-type-specific transcription of the peripherin gene in a subset of neuronal cells. PER1 also identifies a novel neuron-specific transcription factor.