Intron 1 is required for cell type-specific, but not injury-responsive, peripherin gene expression

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Peripheral nervous system (PNS) neurons possess significant regenerative capabilities after injury.
• Gene regulation is critical for this nerve regeneration process, but the underlying mechanisms are not fully understood.
• The peripherin gene, essential for PNS neuron function, is activated after nerve injury.

Purpose of the Study:

• To identify the specific genomic elements controlling the cell-type-specific and injury-induced expression of the peripherin gene in adult mice.
• To elucidate the role of intragenic regions, particularly introns, in regulating peripherin gene expression.

Main Methods:

• Generation of transgenic mice expressing peripherin with deleted introns.
• Analysis of peripherin transgene expression in different tissues and after nerve injury.
• Investigation of transcription factor binding to intron 1 using protein extracts.

Main Results:

• Deletion of introns 2-8 did not affect cell-type-specific or injury-specific peripherin expression.
• Intron 1 was found to bind Sp1 transcription-related proteins differentially in expressing versus non-expressing tissues.
• Transgenes lacking intron 1 showed reduced expression in many PNS neurons and impaired injury-induced activation.

Conclusions:

• Intron 1 contains critical elements for cell type-specific peripherin gene expression in the PNS.
• Sequences in the 5' flanking region, in addition to intron 1, are likely required for activating peripherin gene expression following nerve injury.