title: Regulation of the expression of peptidylarginine deiminase type II gene (PADI2) in human keratinocytes involves Sp1 and Sp3 transcription factors.
abstract: Peptidylarginine deiminases (PAD) convert protein-bound arginine residues into citrulline residues in a Ca(2+) ion-dependent manner. Among the five isoforms (PAD1, 2, 3, 4, and 6) existing in rodents and humans, PAD2 is the most widely expressed in both species, tissues, and organs. In order to study the mechanisms regulating the expression of the human PAD2 gene, PADI2, we characterized its promoter region using transfected human keratinocytes. A series of reporter gene constructions derived from the 2 kb region upstream of the transcription initiation site defined a minimal promoter sequence from nucleotides -132 to -41. This PADI2 region is GC-rich and lacks canonical TATA and CAAT boxes. Investigation of cis-acting elements in the region, further deletion analyses and electrophoretic mobility shift assays using specific antibodies revealed four Sp1-binding sites and identified Sp1 and Sp3 as binding factors important for the promoter activity. These results suggest that Sp1/Sp3 cooperation may provide a mechanism to control the transcription of PADI2.
authors.affiliation: Department of Applied Biological Resource Sciences, School of Agriculture, Ibaraki University, Ami-machi, Inashiki-gun, Ibaraki, Japan.
authors.forename: Sijun
authors.initials: S
authors.lastname: Dong
authors.forename: Toshio
authors.initials: T
authors.lastname: Kojima
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shiraiwa
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Méchin
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chavanas
authors.forename: Guy
authors.initials: G
authors.lastname: Serre
authors.forename: Michel
authors.initials: M
authors.lastname: Simon
authors.forename: Akira
authors.initials: A
authors.lastname: Kawada
authors.forename: Hidenari
authors.initials: H
authors.lastname: Takahara
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D015603:Keratinocytes / Q000201:enzymology*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases; D016329:Sp1 Transcription Factor / Q000502:physiology*; D051705:Sp3 Transcription Factor; D014157:Transcription Factors / Q000502:physiology*; D024363:Transcription Initiation Site
chemical_list: D004268:DNA-Binding Proteins; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D051705:Sp3 Transcription Factor; D006867:Hydrolases; C000620352:PADI2 protein, human; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases