Regulation of the expression of peptidylarginine deiminase type II gene (PADI2) in human keratinocytes involves Sp1 and Sp3 transcription factors.
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.
T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T22 T23 T24 T2 T3 T4 T5 T6 T7 T8 T9
GENE-Y GENE-N GENE-Y GENE-N GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-Y CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL CHEMICAL GENE-N GENE-Y GENE-N GENE-Y GENE-N GENE-Y
PADI2 transcription initiation site PADI2 TATA CAAT boxes cis-acting elements Sp1-binding sites Sp1 Sp3 Sp1 Ca(2+) Sp3 Sp1 Sp3 peptidylarginine deiminase type II PADI2 arginine citrulline Peptidylarginine deiminases PADI2 PAD1, 2, 3, 4, and 6 PAD2 PAD human PAD2