Abstract
The methylation patterns of genes expressed in the mouse male germ line have been examined. Int-1, Hox-2.1, and Prm-1, all of which contain 5' CpG islands, were found to be completely unmethylated at many sites in these domains, both in somatic tissues and in sperm DNA. Many other testis-specific genes have a similar structure and are probably also constitutively unmethylated. Pgk-2, a non-CpG-island gene, is similar to somatic tissue-specific genes in that it is highly methylated in nonexpressing cell types but undermethylated in pachytene spermatocytes and round spermatids, where it is actively transcribed. At later stages of spermatogenesis, however, the gene becomes remethylated and thus acquires the full modification pattern in sperm DNA. In all these cases, the sperm DNA that emerges from the testis does not contain any germ-line-specific unmethylated sites and thus carries the methylation pattern typical of that in somatic tissues.
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Selected References
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- Becker P. B., Ruppert S., Schütz G. Genomic footprinting reveals cell type-specific DNA binding of ubiquitous factors. Cell. 1987 Nov 6;51(3):435–443. doi: 10.1016/0092-8674(87)90639-8. [DOI] [PubMed] [Google Scholar]
- Bird A. P. CpG-rich islands and the function of DNA methylation. Nature. 1986 May 15;321(6067):209–213. doi: 10.1038/321209a0. [DOI] [PubMed] [Google Scholar]
- Bishop C. E., Hatat D. Molecular cloning and sequence analysis of a mouse Y chromosome RNA transcript expressed in the testis. Nucleic Acids Res. 1987 Apr 10;15(7):2959–2969. doi: 10.1093/nar/15.7.2959. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boer P. H., Adra C. N., Lau Y. F., McBurney M. W. The testis-specific phosphoglycerate kinase gene pgk-2 is a recruited retroposon. Mol Cell Biol. 1987 Sep;7(9):3107–3112. doi: 10.1128/mcb.7.9.3107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cedar H. DNA methylation and gene activity. Cell. 1988 Apr 8;53(1):3–4. doi: 10.1016/0092-8674(88)90479-5. [DOI] [PubMed] [Google Scholar]
- Cole K. D., Kandala J. C., Kistler W. S. Isolation of the gene for the testis-specific H1 histone variant H1t. J Biol Chem. 1986 Jun 5;261(16):7178–7183. [PubMed] [Google Scholar]
- Driscoll D. J., Migeon B. R. Sex difference in methylation of single-copy genes in human meiotic germ cells: implications for X chromosome inactivation, parental imprinting, and origin of CpG mutations. Somat Cell Mol Genet. 1990 May;16(3):267–282. doi: 10.1007/BF01233363. [DOI] [PubMed] [Google Scholar]
- Fischman K., Edman J. C., Shackleford G. M., Turner J. A., Rutter W. J., Nir U. A murine fer testis-specific transcript (ferT) encodes a truncated Fer protein. Mol Cell Biol. 1990 Jan;10(1):146–153. doi: 10.1128/mcb.10.1.146. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fung Y. K., Shackleford G. M., Brown A. M., Sanders G. S., Varmus H. E. Nucleotide sequence and expression in vitro of cDNA derived from mRNA of int-1, a provirally activated mouse mammary oncogene. Mol Cell Biol. 1985 Dec;5(12):3337–3344. doi: 10.1128/mcb.5.12.3337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldman D. S., Kiessling A. A., Millette C. F., Cooper G. M. Expression of c-mos RNA in germ cells of male and female mice. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4509–4513. doi: 10.1073/pnas.84.13.4509. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Groudine M., Conkin K. F. Chromatin structure and de novo methylation of sperm DNA: implications for activation of the paternal genome. Science. 1985 May 31;228(4703):1061–1068. doi: 10.1126/science.2986289. [DOI] [PubMed] [Google Scholar]
- Hecht N. B., Bower P. A., Waters S. H., Yelick P. C., Distel R. J. Evidence for haploid expression of mouse testicular genes. Exp Cell Res. 1986 May;164(1):183–190. doi: 10.1016/0014-4827(86)90465-9. [DOI] [PubMed] [Google Scholar]
- Johnson P. A., Peschon J. J., Yelick P. C., Palmiter R. D., Hecht N. B. Sequence homologies in the mouse protamine 1 and 2 genes. Biochim Biophys Acta. 1988 May 6;950(1):45–53. doi: 10.1016/0167-4781(88)90071-1. [DOI] [PubMed] [Google Scholar]
- Keshet I., Lieman-Hurwitz J., Cedar H. DNA methylation affects the formation of active chromatin. Cell. 1986 Feb 28;44(4):535–543. doi: 10.1016/0092-8674(86)90263-1. [DOI] [PubMed] [Google Scholar]
- Kim Y. J., Hwang I., Tres L. L., Kierszenbaum A. L., Chae C. B. Molecular cloning and differential expression of somatic and testis-specific H2B histone genes during rat spermatogenesis. Dev Biol. 1987 Nov;124(1):23–34. doi: 10.1016/0012-1606(87)90455-6. [DOI] [PubMed] [Google Scholar]
- Kleene K. C., Borzorgzadeh A., Flynn J. F., Yelick P. C., Hecht N. B. Nucleotide sequence of a cDNA clone encoding mouse transition protein 1. Biochim Biophys Acta. 1988 Jul 13;950(2):215–220. doi: 10.1016/0167-4781(88)90013-9. [DOI] [PubMed] [Google Scholar]
- Kolsto A. B., Kollias G., Giguere V., Isobe K. I., Prydz H., Grosveld F. The maintenance of methylation-free islands in transgenic mice. Nucleic Acids Res. 1986 Dec 22;14(24):9667–9678. [PMC free article] [PubMed] [Google Scholar]
- Krumlauf R., Holland P. W., McVey J. H., Hogan B. L. Developmental and spatial patterns of expression of the mouse homeobox gene, Hox 2.1. Development. 1987 Apr;99(4):603–617. doi: 10.1242/dev.99.4.603. [DOI] [PubMed] [Google Scholar]
- Lau Y. F., Chan K. M., Sparkes R. Male-enhanced antigen gene is phylogenetically conserved and expressed at late stages of spermatogenesis. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8462–8466. doi: 10.1073/pnas.86.21.8462. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leroy P., Alzari P., Sassoon D., Wolgemuth D., Fellous M. The protein encoded by a murine male germ cell-specific transcript is a putative ATP-dependent RNA helicase. Cell. 1989 May 19;57(4):549–559. doi: 10.1016/0092-8674(89)90125-6. [DOI] [PubMed] [Google Scholar]
- McCarrey J. R., Thomas K. Human testis-specific PGK gene lacks introns and possesses characteristics of a processed gene. Nature. 1987 Apr 2;326(6112):501–505. doi: 10.1038/326501a0. [DOI] [PubMed] [Google Scholar]
- Millan J. L., Driscoll C. E., LeVan K. M., Goldberg E. Epitopes of human testis-specific lactate dehydrogenase deduced from a cDNA sequence. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5311–5315. doi: 10.1073/pnas.84.15.5311. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Monk M., Boubelik M., Lehnert S. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development. 1987 Mar;99(3):371–382. doi: 10.1242/dev.99.3.371. [DOI] [PubMed] [Google Scholar]
- Peschon J. J., Behringer R. R., Brinster R. L., Palmiter R. D. Spermatid-specific expression of protamine 1 in transgenic mice. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5316–5319. doi: 10.1073/pnas.84.15.5316. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ponzetto C., Wolgemuth D. J. Haploid expression of a unique c-abl transcript in the mouse male germ line. Mol Cell Biol. 1985 Jul;5(7):1791–1794. doi: 10.1128/mcb.5.7.1791. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rappold G. A., Stubbs L., Labeit S., Crkvenjakov R. B., Lehrach H. Identification of a testis-specific gene from the mouse t-complex next to a CpG-rich island. EMBO J. 1987 Jul;6(7):1975–1980. doi: 10.1002/j.1460-2075.1987.tb02460.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Romrell L. J., Bellvé A. R., Fawcett D. W. Separation of mouse spermatogenic cells by sedimentation velocity. A morphological characterization. Dev Biol. 1976 Mar;49(1):119–131. doi: 10.1016/0012-1606(76)90262-1. [DOI] [PubMed] [Google Scholar]
- Rubin M. R., Toth L. E., Patel M. D., D'Eustachio P., Nguyen-Huu M. C. A mouse homeo box gene is expressed in spermatocytes and embryos. Science. 1986 Aug 8;233(4764):663–667. doi: 10.1126/science.3726554. [DOI] [PubMed] [Google Scholar]
- Sanford J. P., Clark H. J., Chapman V. M., Rossant J. Differences in DNA methylation during oogenesis and spermatogenesis and their persistence during early embryogenesis in the mouse. Genes Dev. 1987 Dec;1(10):1039–1046. doi: 10.1101/gad.1.10.1039. [DOI] [PubMed] [Google Scholar]
- Schneider-Gädicke A., Beer-Romero P., Brown L. G., Mardon G., Luoh S. W., Page D. C. Putative transcription activator with alternative isoforms encoded by human ZFX gene. Nature. 1989 Dec 7;342(6250):708–711. doi: 10.1038/342708a0. [DOI] [PubMed] [Google Scholar]
- Swain J. L., Stewart T. A., Leder P. Parental legacy determines methylation and expression of an autosomal transgene: a molecular mechanism for parental imprinting. Cell. 1987 Aug 28;50(5):719–727. doi: 10.1016/0092-8674(87)90330-8. [DOI] [PubMed] [Google Scholar]
- Trasler J. M., Hake L. E., Johnson P. A., Alcivar A. A., Millette C. F., Hecht N. B. DNA methylation and demethylation events during meiotic prophase in the mouse testis. Mol Cell Biol. 1990 Apr;10(4):1828–1834. doi: 10.1128/mcb.10.4.1828. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willison K. R., Dudley K., Potter J. Molecular cloning and sequence analysis of a haploid expressed gene encoding t complex polypeptide 1. Cell. 1986 Mar 14;44(5):727–738. doi: 10.1016/0092-8674(86)90839-1. [DOI] [PubMed] [Google Scholar]
- Yagi M., Gelinas R., Elder J. T., Peretz M., Papayannopoulou T., Stamatoyannopoulos G., Groudine M. Chromatin structure and developmental expression of the human alpha-globin cluster. Mol Cell Biol. 1986 Apr;6(4):1108–1116. doi: 10.1128/mcb.6.4.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Ooyen A., Nusse R. Structure and nucleotide sequence of the putative mammary oncogene int-1; proviral insertions leave the protein-encoding domain intact. Cell. 1984 Nov;39(1):233–240. doi: 10.1016/0092-8674(84)90209-5. [DOI] [PubMed] [Google Scholar]