TDP-43 is a transcriptional repressor: the testis-specific mouse acrv1 gene is a TDP-43 target in vivo.

ABSTRACT: TDP-43 is an evolutionarily conserved ubiquitously expressed DNA/RNA-binding protein. Although recent studies have shown its association with a variety of neurodegenerative disorders, the function of TDP-43 remains poorly understood. Here we address TDP-43 function using spermatogenesis as a model system. We previously showed that TDP-43 binds to the testis-specific mouse acrv1 gene promoter in vitro via two GTGTGT-motifs and that mutation of these motifs led to premature transcription in spermatocytes of an otherwise round spermatid-specific promoter. The present study tested the hypothesis that TDP-43 represses acrv1 gene transcription in spermatocytes. Plasmid chromatin immunoprecipitation demonstrated that TDP-43 binds to the acrv1 promoter through GTGTGT motifs in vivo. Reporter gene

SUBMITTER: Lalmansingh AS 

PROVIDER: S-EPMC3064152 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature