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J. Biol. Chem., Vol. 276, Issue 22, 18653-18656, June 1, 2001
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,
,
From UPR 9023 CNRS-Centre CNRS-INSERM de
Pharmacologie-Endocrinologie-141, rue de la Cardonille, 34094 Montpellier Cedex 05, France and ¶ Wessex Regional Genetics
Laboratory, Salisbury District Hospital, Salisbury,
Wiltshire SP2 8BJ, United Kingdom
ZAC is a recently isolated zinc
finger protein that induces apoptosis and cell
cycle arrest. The corresponding gene is imprinted maternally through an unknown mechanism and maps to 6q24-q25, within
the minimal interval harboring the gene responsible for transient
neonatal diabetes mellitus (TNDM) and a tumor suppressor gene involved
in breast cancer. Because of its functional properties, imprinting
status, and expression pattern in mammary cell lines and tumors,
ZAC is the best candidate so far for both disease conditions. In the present work, we delineated ZAC genomic
organization and mapped its transcriptional start site. It is
noteworthy that the ZAC promoter localized to the CpG
island harboring the methylation imprint associated with TNDM and
methylation of this promoter silenced its activity. These data indicate
that the methylation mark may have a direct effect on the silencing of
the ZAC imprinted allele. Our findings further strengthen
the hypothesis that ZAC is the gene responsible for TNDM
and suggest a novel mechanism for ZAC inactivation in
breast tumors.
Recipient of postdoctoral fellowships from the Ministère
des Affaires Etrangères and the Fondation pour la Recherche
Médicale.
To whom correspondence should be addressed. Tel.:
33-467 142 963; Fax: 33-467 542 432; E-mail:
varrault@ccipe.montp.inserm.fr.
This article has been cited by other articles:
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