title: Characterization of the human PANK2 promoter.
abstract: Pantothenate 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.
authors.affiliation: Molecular and Medical Genetics, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA. polsterb@ohsu.edu
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Polster
authors.forename: Moon Y
authors.initials: MY
authors.lastname: Yoon
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Hayflick
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D004247:DNA; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D040901:Proteomics; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D004247:DNA; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase