The detailed entries of the Imprinted Gene Catalogue database were created by Benjamin Tycko, Columbia University, New York and are updated by Ian Morison


 

Detailed entry for Gene:

Zac
Lot1
PLAGL1

Chromosome:

Human Chr6q24-q26
Mouse Chr10 (proximal)

Links:

OMIM

Imprinting:

The maternal allele of Zac is repressed; paternal allele expressed in multiple fetal and adult mouse tissues (Piras G et al, 2000; Kamiya M et al, 2000)

Gene Product:

Zac encodes a zinc finger DNA binding protein (Abdollahi A et al, 1997; Varrault A et al, 1998).

Functional Data:

The Zac gene is regulated by neuropeptides, and it is anti-proliferative (G1 arrest and apoptosis) in transfections (Varrault A et al, 1998; Abdollahi A et al, 1999; Bilanges B et al, 2001). Expression of this gene is lost on transformation of ovarian cells (Abdollahi A et al, 1997) and in breast cancers (Bilanges B et al, 1999) and non-functioning pituitary adenomas (Pagotto U et al, 2000). The ZAC/PLAGL1 gene maps to a region of frequent loss of heterozygosity in human cancers, and Zac protein is thought to be synergistic with the p53 tumor suppressor in causing apoptosis, possibly by co-activation of p53 target genes (Varrault A et al, 1998; Ciani E et al, 1999; Huang SM et al, 2001).
ZAC/PLAG1 is considered a candidate gene for transient neonatal diabetes mellitus (TNDM) caused by pat-UPD6 or trisomy of Chr6q24. TNDM is a rare disorder diagnosed by intrauterine growth retardation and neonatal failure to thrive, dehydration and insulin-requiring hyperglycemia within the first month of life. In this connection, it was pointed out that ZAC / PLAGL1 is a transcriptional regulator of the type 1 receptor for pituitary adenylate cyclase-activating polypeptide, which is a potent insulin secretagog and an important mediator of autocrine control of insulin secretion in the pancreatic islet (Kamiya M et al, 2000). A differentially methylated region in the ZAC locus was found to be demethylated in some non-UPD cases of TNDM (Arima T et al, 2001).

 

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