Necdin is a growth suppressor expressed in virtually all postmitotic neurons in the brain. The human necdin gene, NDN, is maternally imprinted and deleted in the Prader-Willi syndrome, a neurobehavioral contiguous gene disorder. Here, we isolated and characterized the human chromosomal necdin gene and its promoter region. The necdin gene is intronless, and it encodes a protein of 321 amino acid residues, four residues shorter than mouse Necdin. By fluorescence in-situ hybridization analysis, the necdin gene was localized to chromosome 15q11.2-q12 within the Prader-Willi syndrome deletion region. CpG islands were found in a region extending from the proximal 5'-flanking sequence to the protein coding region. The 5'-flanking sequence, which lacks canonical TATA and CAAT boxes, possessed a promoter activity in postmitotic neurons derived from murine embryonal carcinoma P19 cells. Methylation in vitro of HhaI CpG sites in the promoter region reduced the transcriptional activity. These results suggest that the necdin gene is silenced through methylation of the CpG island encompassing its promoter region.
Copyright 1998 Elsevier Science B.V. All rights reserved.