Research article

The Prader-Willi syndrome murine imprinting center is not involved in the spatio-temporal transcriptional regulation of the Necdin gene

Françoise Watrin¹ , Elodie Le Meur¹ , Nathalie Roeckel² , Marie-Anne Ripoche³ , Luisa Dandolo³ and Françoise Muscatelli¹

¹  Centre National de la Recherche Scientifique UMR 6156, IBDM, Parc scientifique de Luminy, Case 907, 13288 Marseille Cedex 9, France

²  Institut National de la Santé et de la Recherche Médicale UMR491, IPHM, Faculté de Médecine de la Timone, 27 Bd. J. Moulin, 13385 Marseille Cedex 5, France

³  Département de Développement, Génétique et Pathologie Moléculaire, Institut Cochin, 24 rue du Faubourg St Jacques, 75014 Paris, France

author email corresponding author email

BMC Genetics 2005, 6:1doi:10.1186/1471-2156-6-1

Published:	5 January 2005

Abstract

Background

The human Prader-Willi syndrome (PWS) domain and its mouse orthologue include a cluster of paternally expressed genes which imprinted expression is co-ordinately regulated by an imprinting center (IC) closely associated to the Snurf-Snrpn gene. Besides their co-regulated imprinted expression, two observations suggest that the spatio-temporal expression of these genes could also be co-regulated. First, the PWS genes have all been reported to be expressed in the mouse nervous system. Second, Snurf-Snrpn and its associated IC are the most ancient elements of the domain which later acquired additional functional genes by retrotransposition. Although located at least 1.5 megabases from the IC, these retroposons acquired the same imprinted regulation as Snurf-Snrpn. In this study, we ask whether the IC, in addition to its function in imprinting, could also be involved in the spatio-temporal regulation of genes in the PWS domain.

Results

We compared the expression pattern of Snurf-Snrpn and C/D-box small nucleolar RNAs (snoRNAs) MBII-85 and MBII-52 to the expression pattern of the two evolutionary related retroposons Ndn and Magel2, in the developing mouse embryo. We show that these genes have highly similar expression patterns in the central nervous system, suggesting that they share a common central nervous system-specific regulatory element. Among these genes, Ndn and Magel2 display the most similar expression patterns. Using transgenic mice containing the Ndn and Magel2 genes, we show that the transgenic Ndn gene whereas not imprinted is correctly expressed. Search for DNase I hypersensitive sites in the Ndn-Magel2 genomic region and comparative genomic analyses were performed in order to identify potential transcriptional cis-regulatory elements.

Conclusions

These results strongly suggest that paternally expressed genes of the PWS domain share a common central nervous system-specific regulatory element. We proposed that this regulatory element could co-localize with the IC. However, we demonstrate that the IC, if required for imprinted regulation, is not involved in the spatio-temporal regulation of distantly located retrotransposed genes such as the Ndn gene in the PWS domain.