The cell cycle control gene ZAC/PLAGL1 is imprinted - a strong candidate gene for transient neonatal diabetes

Citation
M. Kamiya et al., The cell cycle control gene ZAC/PLAGL1 is imprinted - a strong candidate gene for transient neonatal diabetes, HUM MOL GEN, 9(3), 2000, pp. 453-460
Citations number
36
Categorie Soggetti
Molecular Biology & Genetics
Journal title
HUMAN MOLECULAR GENETICS
ISSN journal
09646906 → ACNP
Volume
9
Issue
3
Year of publication
2000
Pages
453 - 460
Database
ISI
SICI code
0964-6906(20000212)9:3<453:TCCCGZ>2.0.ZU;2-0
Abstract
We describe a screen for new imprinted human genes, and the identification in this way of ZAC (zinc finger protein which regulates apoptosis and cell cycle arrest)/PLAGL1 (pleomorphic adenoma of the salivary gland gene like 1 )as a strong candidate gene for transient neonatal diabetes mellitus (TNDM) . To screen for imprinted genes, we compared parthenogenetic DNA from the c himeric patient FD and androgenetic DNA from hydatidiform mole, using restr iction landmark genome scanning for methylation. This resulted in identific ation of two novel imprinted loci, one of which (NV149) we mapped to the TN DM region of 6q24. From analysis of the corresponding genomic region, it wa s determined that NV149 lies similar to 60 kb upstream of the ZAC/PLAGL1 ge ne. RT-PCR analysis was used to confirm that this ZAC/PLAGL1 is expressed o nly from the paternal allele in a variety of tissues. TNDM is known to resu lt from upregulation of a paternally expressed gene on chromosome 6q24. The paternal expression, map position and known biological properties of ZAC/P LAGL1 make it highly likely that it is the TNDM gene. In particular, ZAC/PL AGL1 is a transcriptional regulator of the type 1 receptor for pituitary ad enylate cyclase-activating polypeptide, which is the most potent known insu lin secretagog and an important mediator of autocrine control of insulin se cretion in the pancreatic islet.