HGSNAT has a TATA-less promoter with multiple starts of transcription

Promoter fragments in antisense orientation (constructs pGL4 − 20/− 1305 and pGL4 + 50/− 1305) led to reporter activities of about 50% of the pGL4 − 1305/− 20 activity, implying divergent initiation of transcription at the promoter. We identified two main TSSs at positions + 1 and − 15 from DS-ATG using Rapid amplification of cDNA ends (5′RACE). Transcripts initiating at the TSSs thus contain only DS-ATG. Five patients from our MPS IIIC cohort (n = 23) carried the rs4523300 promoter variant and one the rs149596192 promoter variant. Both variants lowered the expression of the reporter down to 68% and 59%, respectively. However, white blood cell (WBC) N-acetyltransferase activities in individuals carrying the variants did not significantly differ from homozygotes for the wild-type alleles, suggesting only a partial impact of transcriptional regulation on N-acetyltransferase activities in vivo.