Characterization of the human PANK2 promoter

ABSTRACTPantothenate kinase 2 (PANK2) is an essential regulatory enzyme in coenzyme A biosynthesis. PANK2 mutations cause pantothenate kinase-associated neurodegeneration (PKAN), which leads to pigmentary retinopathy, progressive dystonia and other abnormalities. Two nearly identical PANK2 isoforms have been described: short PANK2 and mature PANK2, which are processed from a precursor isoform. Since the biological relevance of these isoforms remains unclear, we sought to explore their transcriptional regulation. Here we show that their regulation is distinct and describe a promoter for the short isoform of PANK2. Moreover, we identify potential regulators of PANK2 expression, including NF-Y, FOXN4 and the human heterogeneous nuclear ribonucleoprotein A/B family. These findings validate expression of the short PANK2 isoform and enable predictions about potentially deleterious sequence variants in the regulatory region of this human disease gene.