Promoter-Specific Expression of the Imprinted IGF2 Gene in Cattle (Bos taurus)1

Abstract The domestic cattle (Bos taurus) has been a good animal model for embryo biotechnologies, such as in vitro fertilization and nuclear transfer. However, animals produced from these technologies often suffer from large-calf syndrome, suggesting fetal growth disregulation. The product of the insulin-like growth factor 2 (IGF2) gene is one of the most important fetal mitogens known to date. A detailed analysis of age-, tissue-, and allele-specific expression of IGF2 has not been performed in the bovine mainly because the majority of the bovine sequence has been unavailable. In the present study, we obtained virtually the entire sequence of the bovine IGF2 cDNA, identified expressed single-nucleotide polymorphisms (SNPs) in both exons 3 and 10, and determined the age-, tissue-, and promoter-specific expression of bovine IGF2 in fetal, calf, and adult tissues. We found that, similar to the human and mouse, bovine IGF2 is subjected to extensive transcriptional regulation through multiple promoters, alternative splicing and polyadenylation, as well as genetic imprinting. However, major differences were found in the regulation of the bovine IGF2 in nearly all aspects of age-, tissue-, promoter-, and allele-specific expression of IGF2, and the promoter-specific loss of imprinting from every other species studied, including cattle's close relatives, the sheep and the pig. The data presented here are of important reference value to cattle produced from embryo biotechnologies.

[1]  J. Womack,et al.  Conservation of genomic imprinting at the XIST, IGF2, and GTL2 loci in the bovine , 2004, Mammalian Genome.

[2]  M. O’Neill,et al.  Genomic Imprinting of H19 in Naturally Reproduced and Cloned Cattle1 , 2004, Biology of reproduction.

[3]  C. Long,et al.  Epigenetic and Genomic Imprinting Analysis in Nuclear Transfer Derived Bos gaurus/Bos taurus Hybrid Fetuses1 , 2004, Biology of reproduction.

[4]  W. Reik,et al.  Placental-specific insulin-like growth factor 2 (Igf2) regulates the diffusional exchange characteristics of the mouse placenta. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J. Deakin,et al.  The monotreme genome: a patchwork of reptile, mammal and unique features? , 2003, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[6]  S. Schmutz,et al.  Linkage mapping of IGF2 on cattle chromosome 29. , 2003, Animal genetics.

[7]  S. Murphy,et al.  Imprinting evolution and the price of silence. , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[8]  M. Georges,et al.  Comparative sequence analysis of the INS–IGF2–H19 gene cluster in pigs , 2002, Mammalian Genome.

[9]  W. Reik,et al.  Placental-specific IGF-II is a major modulator of placental and fetal growth , 2002, Nature.

[10]  J. Killian,et al.  Monotreme IGF2 expression and ancestral origin of genomic imprinting. , 2001, The Journal of experimental zoology.

[11]  V. Han,et al.  Spatial and temporal patterns of expression of messenger RNA for insulin-like growth factors and their binding proteins in the placenta of man and laboratory animals. , 2000, Placenta.

[12]  J. Byrd,et al.  M6P/IGF2R imprinting evolution in mammals. , 2000, Molecular cell.

[13]  Leif Andersson,et al.  A paternally expressed QTL affecting skeletal and cardiac muscle mass in pigs maps to the IGF2 locus , 1999, Nature Genetics.

[14]  D. Choudhury,et al.  A conserved structural element in horse and mouse IGF2 genes binds a methylation sensitive factor. , 1998, Nucleic acids research.

[15]  T. Moore,et al.  Multiple imprinted sense and antisense transcripts, differential methylation and tandem repeats in a putative imprinting control region upstream of mouse Igf2. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[16]  T. Ekström,et al.  Expression levels of the insulin-like growth factor-II gene (IGF2) in the human liver: developmental relationships of the four promoters. , 1996, The Journal of endocrinology.

[17]  M. Loda,et al.  Detection of p53 Mutations by Single‐strand Conformation Polymorphisms (SSCP) Gel Electrophoresis: A Comparative Study of Radioactive and Nonradioactive Silver‐stained SSCP Analysis , 1995, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

[18]  T. Ekström,et al.  Promoter-specific IGF2 imprinting status and its plasticity during human liver development. , 1995, Development.

[19]  A. Hoffman,et al.  Promoter-specific imprinting of the human insulin-like growth factor-II gene , 1994, Nature.

[20]  S. Davies.  Developmental regulation of genomic imprinting of the IGF2 gene in human liver. , 1994, Cancer research.

[21]  K. Lugenbeel,et al.  Characterization of the linked ovine insulin and insulin-like growth factor-II genes. , 1994, DNA and cell biology.

[22]  T. Ekström,et al.  Overlapping patterns of IGF2 and H19 expression during human development: biallelic IGF2 expression correlates with a lack of H19 expression. , 1994, Development.

[23]  M. Binoux,et al.  Developmental regulation of bovine insulin-like growth factor-II (IGF-II) gene expression: homology between bovine transcripts and human IGF-II exons. , 1993, Journal of molecular endocrinology.

[24]  C. Polychronakos,et al.  Parental genomic imprinting of the human IGF2 gene , 1993, Nature Genetics.

[25]  M. Bartolomei,et al.  Physical linkage of two mammalian imprinted genes, H19 and insulin–like growth factor 2 , 1992, Nature genetics.

[26]  F. V. Schaik,et al.  Initial characterization of the four promoters of the human insulin-like growth factor II gene , 1991, Molecular and Cellular Endocrinology.

[27]  A. Efstratiadis,et al.  Parental imprinting of the mouse insulin-like growth factor II gene , 1991, Cell.

[28]  D. Straus,et al.  The E-domain peptide of rat pro-insulin-like growth factor II (proIGF-II): properties of the peptide in serum and production by rat cell lines. , 1990, Biochimica et biophysica acta.

[29]  T. Sekiya,et al.  Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[30]  T. Ekström,et al.  Overlapping patterns of IGF 2 and H 19 expression during human development : biallelic IGF 2 expression correlates with a lack of H 19 expression , 2022 .