Human transcription factor genes involved in neuronal development tend to have high GC content and CpG elements in the proximal promoter region

Transcription factors (TFs) play critical roles in the development of the nervous system, but the transcriptional regulatory mechanisms of these genes are poorly understood. Here we analyzed 5-kb of the 5′ flanking genomic DNA sequences of 41 TF genes involved in neuronal development. The results showed that the TF genes tend to have higher GC contents in the proximal region and most of the TF genes have at least one proximal GC-rich (GC content > 60%) promoter with a CpG island. The promoter distribution analysis showed that the GC-poor promoters were sporadically distributed within the 5-kb flanking genomic sequence (FGS); however, more than half (37 of 70) of the GC-rich promoters were located in the proximal region between nucleotides −1 and −500. Luciferase assays showed that partial GC-rich promoters increased gene expression in SH-SY5Y cells and that CpG methylation repressed the promoter activity. This study suggests a potential general mechanism for regulation of TF expression.