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Characterization of the methylation-sensitive promoter of the imprinted ZAC gene supports its role in transient neonatal diabetes mellitus

Characterization of the methylation-sensitive promoter of the imprinted ZAC gene supports its role in transient neonatal diabetes mellitus
Characterization of the methylation-sensitive promoter of the imprinted ZAC gene supports its role in transient neonatal diabetes mellitus
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.
0021-9258
18653-18656
Varrault, A.
a4297e76-ec09-4566-bfea-91fc81508294
Bilanges, B.
7b5f6dcc-50bb-4db3-9ee7-a5ac26eeb21b
Mackay, D.J.
588a653e-9785-4a00-be71-4e547850ee4a
Basyuk, E.
db1a1e1f-2305-4be8-9a92-80e106839a35
Ahr, B.C.
550f6e9c-fa7e-4ab6-ae36-643f2d9f457f
Fernandez, C.
ebc210ab-d054-4066-a171-dfd341854e8e
Robinson, D.O.
6b7e8cdc-b9c4-4ecf-a344-1bf0ae990f8a
Bockaert, J.
614521d2-f228-479a-88f0-60a178b17a6b
Journot, L.
31d93b9c-faa8-413a-951a-35a5d31c98cb
Varrault, A.
a4297e76-ec09-4566-bfea-91fc81508294
Bilanges, B.
7b5f6dcc-50bb-4db3-9ee7-a5ac26eeb21b
Mackay, D.J.
588a653e-9785-4a00-be71-4e547850ee4a
Basyuk, E.
db1a1e1f-2305-4be8-9a92-80e106839a35
Ahr, B.C.
550f6e9c-fa7e-4ab6-ae36-643f2d9f457f
Fernandez, C.
ebc210ab-d054-4066-a171-dfd341854e8e
Robinson, D.O.
6b7e8cdc-b9c4-4ecf-a344-1bf0ae990f8a
Bockaert, J.
614521d2-f228-479a-88f0-60a178b17a6b
Journot, L.
31d93b9c-faa8-413a-951a-35a5d31c98cb

Varrault, A., Bilanges, B., Mackay, D.J., Basyuk, E., Ahr, B.C., Fernandez, C., Robinson, D.O., Bockaert, J. and Journot, L. (2001) Characterization of the methylation-sensitive promoter of the imprinted ZAC gene supports its role in transient neonatal diabetes mellitus. The Journal of Biological Chemistry, 276 (22), 18653-18656. (doi:10.1074/jbc.C100095200).

Record type: Article

Abstract

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.

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Published date: 1 June 2001
Additional Information: Accelerated publication

Identifiers

Local EPrints ID: 25010
URI: http://eprints.soton.ac.uk/id/eprint/25010
ISSN: 0021-9258
PURE UUID: ad24e48c-568c-4751-980c-a656dec9921e
ORCID for D.J. Mackay: ORCID iD orcid.org/0000-0003-3088-4401

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Date deposited: 05 Apr 2006
Last modified: 17 Dec 2019 01:54

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Contributors

Author: A. Varrault
Author: B. Bilanges
Author: D.J. Mackay ORCID iD
Author: E. Basyuk
Author: B.C. Ahr
Author: C. Fernandez
Author: D.O. Robinson
Author: J. Bockaert
Author: L. Journot

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