{'fraction_non_alphanumeric': 0.019164955509924708, 'fraction_numerical': 0.01779603011635866, 'mean_word_length': 5.675799086757991, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Low affinity neurotrophin receptor (p75NTR) expression is regulated by early growth response (Egr) transcriptional regulators

Egr transcriptional regulators are rapidly induced by a variety of extracellular stimuli that influence cellular growth and differentiation. Egr proteins (Egr1–4) modulate gene expression by binding to response elements in target gene promoters to facilitate their transactivation. However, very few target genes have been shown to require Egr‐mediated transcription in vivo. The low affinity neurotrophin receptor (p75NTR) was identified as a potential target gene regulated by Egr3 in a recent microarray analysis, suggesting that Egr3 may have a role in modulating neurotrophin signaling. The p75NTR promoter lacks consensus TATA and CAAT sequences but contains multiple GC‐rich motifs, raising the possibility that Egr proteins may directly transactivate p75NTR expression. In this study, we show that both Egr1 and Egr3 bind and transactivate p75NTR promoter in vitro and in vivo. Moreover, Egr1 and Egr3 activate transcription through distinct response elements in the p75NTR promoter and Egr3, but not Egr1, appears to play a critical role in promoter transactivation. Accordingly, p75NTR expression is deregulated in muscle spindles and sciatic nerves in the absence of both Egr1 and Egr3 in vivo. These results elucidate a new mechanism whereby Egr proteins can modulate neurotrophin signaling during development and disease.