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Molecular and Cellular Biology, November 2003, p. 8345-8351, Vol. 23, No. 22
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.22.8345-8351.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Functional Characterization of a Testis-Specific DNA Binding Activity at the H19/Igf2 Imprinting Control Region

Aaron B. Bowman, John M. Levorse, Robert S. Ingram, and Shirley M. Tilghman^*

Howard Hughes Medical Institute and Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544

Received 13 May 2003/ Returned for modification 10 July 2003/ Accepted 7 August 2003

The DNA methylation state of the H19/Igf2 imprinting control region (ICR) is differentially set during gametogenesis. To identify factors responsible for the paternally specific DNA methylation of the ICR, germ line and somatic extracts were screened for proteins that bind to the ICR in a germ line-specific manner. A specific DNA binding activity that was restricted to the male germ line and enriched in neonatal testis was identified. Its three binding sites within the ICR are very similar to the consensus sequence for nuclear receptor extended half sites. To determine if these binding sites are required for establishment of the paternal epigenetic state, a mouse strain in which the three sites were mutated was generated. The mutated ICR was able to establish a male-specific epigenetic state in sperm that was indistinguishable from that established by the wild-type ICR, indicating that these sequences are either redundant or have no function. An analysis of the methylated state of the mutant ICR in the soma revealed no differences from the wild-type ICR but did uncover in both mutant and wild-type chromosomes a significant relaxation in the stringency of the methylated state of the paternal allele and the unmethylated state of the maternal allele in neonatal and adult tissues.

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* Corresponding author. Mailing address: Howard Hughes Medical Institute and Department of Molecular Biology, Princeton University, Princeton, NJ 08544. Phone: (609) 258-6100. Fax: (609) 258-1615. E-mail: smt{at}princeton.edu.

Present address: Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030.

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Molecular and Cellular Biology, November 2003, p. 8345-8351, Vol. 23, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.22.8345-8351.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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