The initiation of transcription is accomplished via interactions of many different proteins with common and gene-specific regulatory motifs. Clearly, sequence-specific transcription factors play a crucial role in the specificity of transcription initiation. A group of sequence-specific DNA-binding proteins, related to the transcription factor Sp1, has been implicated in the regulation of many different genes, since binding sites for these transcription factors (GC/GT boxes) are a recurrent motif in regulatory sequences such as promoters, enhancers and CpG islands of these genes. The simultaneous occurrence of several homologous GC/GT box-binding factors precludes a straightforward deduction of their role in transcriptional regulation. In this review, we focus on the connection between functional specificity and biochemical properties including glycosylation, phosphorylation and acetylation of Sp1-related factors.