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RESEARCH ARTICLE

Expression of imprinted genes surrounding the callipyge mutation in ovine skeletal muscle

T. Vuocolo A , N. E. Cockett B and R. L. Tellam A C
+ Author Affiliations
- Author Affiliations

A CSIRO Livestock Industries, Queensland Biosciences Precinct, 306 Carmody Road, St Lucia, Qld 4067, Australia.

B Utah State University, Logan, Utah, USA.

C Corresponding author. Email: Ross.Tellam@csiro.au

Australian Journal of Experimental Agriculture 45(8) 879-892 https://doi.org/10.1071/EA05049
Submitted: 14 February 2005  Accepted: 3 June 2005   Published: 26 August 2005

Abstract

The callipyge mutation in sheep results in postnatal hypertrophy and leanness of skeletal muscles in the pelvic limbs and loins. Associated changes also occur in the expression of a number of imprinted genes flanking the site of the mutation, which lies at the telomeric end of ovine chromosome 18. The transcripts from several of these genes are either spliced or undergo substantial RNA processing, sometimes in a very complex manner. The current investigation examined the effects of the callipyge mutation on the relative expression of some of these splice variants in samples taken: at birth, when the muscle hypertrophy phenotype is not expressed; and at 12 weeks of age, when the phenotype is fully apparent. It was concluded that changes in the postnatal developmental expression pattern of Dlk-1 are closely associated with the expression of the phenotype and that the callipyge mutation may promote a fetal-like gene expression program for some genes during postnatal life.

Additional keywords: Dlk-1, GTL2 , PEG11, MEG8.


Acknowledgments

We thank Jason White (University of Western Australia) and Matt McDonagh (Department of Primary Industries, Victoria) for aid in the collection of skeletal muscle samples from sheep. We are also grateful to Tracy Shay Hadfield, Dave Forrester and Sandy Eng (Utah State University) for assistance in sample collection and for providing access to a flock of sheep carrying the callipyge mutation. We also thank Lisa Leeton and Manuela Stolic for stimulating discussions. The research was supported by funds from Meat and Livestock Australia and Australian Wool Innovation through their Sheep Genomics Program. We are also grateful to an anonymous reviewer for insightful comments regarding the measurement of PEG11 and PEG11AS expression.


References


Bidwell CA, Kramer LN, Perkins AC, Hadfield TS, Moody DE, Cockett NE (2004) Expression of PEG11 and PEG11AS transcripts in normal and callipyge sheep. BMC Biology 2, 17–28.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Bidwell CA, Shay TL, Georges M, Beever JE, Berghmans S, Cockett NE (2001) Differential expression of the GTL2 gene within the callipyge region of ovine chromosome 18. Animal Genetics 32, 248–256.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Cavaille J, Seitz H, Paulsen M, Ferguson-Smith AC, Bachellerie JP (2002) Identification of tandemly-repeated C/D snoRNA genes at the imprinted human 14q32 domain reminiscent of those at the Prader-Willi/Angelman syndrome region. Human Molecular Genetics 11, 1527–1538.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Charlier C, Segers K, Karim L, Shay T, Gyapay G, Cockett N, Georges M (2001a) The callipyge mutation enhances the expression of coregulated imprinted genes in cis without affecting their imprinting status. Nature Genetics 27, 367–369.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Charlier C, Segers K, Wagenaar D, Karim L, Berghmans S , et al . (2001b) Human–ovine comparative sequencing of a 250-kb imprinted domain encompassing the callipyge (clpg) locus and identification of six imprinted transcripts: DLK1, DAT, GTL2, PEG11, anti-PEG11, and MEG8.  Genome Research 11, 850–862.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Cockett NE, Jackson SP, Shay TL, Farnir F, Berghmans S, Snowder GD, Nielsen DM, Georges M (1996) Polar overdominance at the ovine callipyge locus. Science 273, 236–238.
PubMed |
open url image1

Cockett NE, Jackson SP, Shay TL, Nielsen D, Moore SS, Steele MR, Barendse W, Green RD, Georges M (1994) Chromosomal localization of the callipyge gene in sheep (Ovis aries) using bovine DNA markers. Proceedings of the National Academy of Sciences of the United States of America 91, 3019–3023.
PubMed |
open url image1

Cockett NE, Shay TL, Smit M (2001) Analysis of the sheep genome. Physiological Genomics 7, 69–78.
PubMed |
open url image1

Cockett NE, Smit MA, Bidwell CA, Segers K, Hadfield TL, Snowder GD, Georges M, Charlier C (2005) The callipyge mutation and other genes that affect muscle hypertrophy in sheep. Genetics, Selection, Evolution. 37, S65–S81.
Crossref | GoogleScholarGoogle Scholar | open url image1

Croteau S, Charron MC, Latham KE, Naumova AK (2003) Alternative splicing and imprinting control of the Meg3/Gtl2-Dlk1 locus in mouse embryos. Mammalian Genome 14, 231–241.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Davis E, Caiment F, Tordoir X, Cavaille J, Ferguson-Smith A, Cockett N, Georges M, Charlier C (2005) RNAi-mediated allelic trans-interaction at the imprinted Rtl1/Peg11 locus. Current Biology 15, 743–749.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Davis E, Jensen CH, Schroder HD, Farnir F, Shay-Hadfield T, Kliem A, Cockett N, Georges M, Charlier C (2004) Ectopic expression of DLK1 protein in skeletal muscle of padumnal heterozygotes causes the callipyge phenotype. Current Biology 14, 1858–1862.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Fazzari MJ, Greally JM (2004) Epigenomics: beyond CpG islands. Nature Reviews. Genetics 5, 446–455.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Freking BA, Keele JW, Nielsen MK, Leymaster KA (1998) Evaluation of the ovine callipyge locus. II. Genotypic effects on growth, slaughter, and carcass traits. Journal of Animal Science 76, 2549–2559.
PubMed |
open url image1

Freking BA, Murphy SK, Wylie AA, Rhodes SJ, Keele JW, Leymaster KA, Jirtle RL, Smith TPL (2002) Identification of the single base change causing the callipyge muscle hypertrophy phenotype, the only known example of polar overdominance in mammals. Genome Research 12, 1496–1506.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Georges M, Charlier C, Cockett N (2003) The callipyge locus: evidence for the trans interaction of reciprocally imprinted genes. Trends in Genetics 19, 248–252.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Han W, Ye Q, Moore MAS (2000) A soluble form of human Delta-like-1 inhibits differentiation of hematopoietic progenitor cells. Blood 95, 1616–1625.
PubMed |
open url image1

Hernandez A, Martinez ME, Croteau W, St Germain DL (2004) Complex organization and structure of sense and antisense transcripts expressed from the DIO3 gene imprinted locus. Genomics 83, 413–424.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Hsiao CC, Huang CC, Sheen JM, Tai MH, Chen CM, Huang LL, Chuang JH (2005) Differential expression of delta-like gene and protein in neuroblastoma, ganglioneuroblastoma and ganglioneuroma. Modern Pathology 18, 656–662.
Crossref | PubMed |
open url image1

Jackson SP, Green RD, Miller MF (1997a) Phenotypic characterization of rambouillet sheep expressing the callipyge gene. I. Inheritance of the condition and production characteristics. Journal of Animal Science 75, 14–18.
PubMed |
open url image1

Jackson SP, Miller MF, Green RD (1997b) Phenotypic characterization of rambouillet sheep expressing the callipyge gene. II. Carcass characteristics and retail yield. Journal of Animal Science 75, 125–132.
PubMed |
open url image1

Jackson SP, Miller MF, Green RD (1997c) Phenotypic characterization of rambouillet sheep expression the callipyge gene. III. Muscle weights and muscle weight distribution. Journal of Animal Science 75, 133–138.
PubMed |
open url image1

Jensen CH, Jauho EI, Santonu-Rugiu E, Holmskov U, Teisner B, Tygstrup N, Bisgaard HC (2004) Transit-amplifying ductular (oval) cells and their hepatocytic progeny are characterized by a novel and distinctive expression of delta-like protein/preadipocyte factor 1/ fetal antigen 1. American Journal of Pathology 164, 1347–1359.
PubMed |
open url image1

Kaneta M, Osawa M, Osawa M, Sudo K, Nakauchi H, Farr AG, Takahama Y (2000) A role for Pref-1 and HES-1 in thymocyte development. Journal of Immunology (Baltimore, Md.: 1950) 164, 256–264.
PubMed |
open url image1

Koohmaraie M, Shackelford SD, Wheeler TL, Lonergan SM, Doumit ME (1995) A muscle hypertrophy condition in lamb (callipyge): characterization of effects on muscle growth and meat quality traits. Journal of Animal Science 73, 3596–3607.
PubMed |
open url image1

Laborda J, Sausville EA, Hoffman T, Notario V (1993) Dlk, a putative mammalian homeotic gene differentially expressed in small cell lung carcinoma and neuroendocrine tumor cell line. The Journal of Biological Chemistry 268, 3817–3820.
PubMed |
open url image1

Lee K, Villena JA, Moon YS, Kim KH, Lee S, Kang C, Sul HS (2003) Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor-1 (Pref-1). The Journal of Clinical Investigation 111, 453–461.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Lin S-P, Youngson N, Takada S, Seitz A, Reik W, Paulsen M, Cavaille J, Ferguson-Smith AC (2003) Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlk1-Gtl2 imprinted cluster on mouse chromosome 2. Nature Genetics 35, 97–102.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Mattick JS (2003) Challenging the dogma: the hidden layer of non-protein coding RNAs in complex organisms. BioEssays 25, 930–939.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Mei B, Zhao L, Chen L, Sul HS (2002) Only the large soluble form of preadipocyte factor-1 (Pref-1), but not the small soluble and membrane forms, inhibits adipocyte differentiation: role of alternative splicing. The Biochemical Journal 364, 137–144.
PubMed |
open url image1

Miyoshi N, Wagatsuma H, Wakana S, Shiroishi T, Nomura M, Aisaka K, Kohda T, Surani MA, Kaneko-Ishino T, Ishino F (2000) Identification of an imprinted gene, MEG3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q. Genes to Cells 5, 211–220.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Moore T, Haig D (1991) Genomic imprinting in mammalian development: a parental tug of war. Trends in Genetics 7, 45–49.
PubMed |
open url image1

Moore KA, Pytowski B, Witte L, Hicklin D, Lemischka IR (1997) Hematopoietic activity of a stromal cell transmembrane protein containing epidermal growth factor-like repeat motifs. Proceedings of the National Academy of Sciences of the United States of America 94, 4011–4016.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Murphy SK, Jirtle RL (2003) Imprinting evolution and the price of silence. BioEssays 25, 577–588.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Murphy SK, Freking BA, Smith TPL, Leymaster K, Nolan CM, Wylie AA, Evans HK, Jirtle RL (2005) Abnormal postnatal maintenance of elevated DLK1 transcript levels in callipyge sheep. Mammalian Genome 16, 171–183.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Ohno N, Izawa A, Hattori M, Kageyama R, Sudo T (2001) DLK inhibits stem cell factor-induced colony formation of murine hematopoietic progenitors: Hes-1-independent effect. Stem Cells (Dayton, Ohio) 19, 71–79.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Paulsen M, Ferguson-Smith AC (2001) DNA methylation in genomic imprinting, development, and disease. The Journal of Pathology 195, 97–110.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Paulsen M, Takada S, Youngson NA, Benchaib M, Charlier C, Segers K, Georges M, Ferguson-Smith AC (2001) Comparative sequence analysis of the imprinted Dlk1-Gtl2 locus in three mammalian species reveals highly conserved genomic elements and refines comparison with the Igf2–H19 region. Genome Research 11, 2085–2094.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Peng CF, Wei Y, Levsky JM, McDonald TV, Childs G, Kitsis RN (2002) Microarray analysis of global changes in gene expression during cardiac myocyte differentiation. Physiological Genomics 9, 145–155.
PubMed |
open url image1

Reik W, Walter J (2001) Genomic imprinting: parental influence on the genome. Nature Reviews. Genetics 2, 21–32.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Schmidt JV, Matteson PG, Jones BK, Guan X-J, Tilghman SM (2000) The DLK1 and GTL2 genes are linked and reciprocally imprinted. Genes & Development 14, 1997–2002.
PubMed |
open url image1

Schuster-Gossler K, Bilinski P, Sado T, Ferguson-Smith A, Gossler A (1998) The mouse Gtl2 gene is differentially expressed during embryonic development, encodes multiple alternatively spliced transcripts, and may act as an RNA. Developmental Dynamics 212, 214–228.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Schuster-Gossler K, Simon-Chazottes D, Guenet JL, Zachgo J, Gossler A (1996) Gtl2lacZ, an insertional mutation on mouse chromosome 12 with parental origin-dependent phenotype. Mammalian Genome 7, 20–24.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Seitz H, Royo H, Bortolin ML, Lin SP, Ferguson-Smith AC, Cavaille J (2004) A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain. Genome Research 14, 1741–1748.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Seitz H, Youngson N, Lin SP, Dalbert S, Paulsen M, Bachellerie JP, Ferguson-Smith AC, Cavaille J (2003) Imprinted microRNA genes transcribed antisense to a reciprocally imprinted retrotransposon-like gene. Nature Genetics 34, 261–262.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Shimoda M, Morita S, Obata Y, Sotomaru Y, Kono T, Hatada I (2002) Imprinting of a small nucleolar RNA gene on mouse chromosome 12. Genomics 79, 483–485.
Crossref | PubMed |
open url image1

Smas CM, Sul HS (1993) Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiation. Cell 73, 725–734.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Smas CM, Chen L, Sul HS (1997) Cleavage of membrane-associated pref-1 generates a soluble inhibitor of adipocyte differentiation. Molecular and Cellular Biology 17, 977–988.
PubMed |
open url image1

Smas CM, Kachinskas D, Liu CM, Xie X, Dircks LK, Sul HS (1998) Transcriptional control of the pref-1 gene in 3T3–L1 adipocyte differentiation. Sequence requirement for differentiation-dependent suppression. The Journal of Biological Chemistry 273, 31751–31758.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Smit M, Segers K, Carrascosa LG, Shay T, Baraldi F, Gyapay G, Snowder G, Georges M, Cockett N, Charlier C (2003) Mosaicism of solid gold supports the causality of a noncoding A-to-G transition in the determinism of the callipyge phenotype. Genetics 163, 453–456.
PubMed |
open url image1

Stalberg P, Grimfjard P, Santesson M, Zhou Y, Lindberg D , et al . (2004) Transfection of the multiple endocrine neoplasia type 1 gene to a human endocrine pancreatic tumor cell line inhibits cell growth and affects expression of JunD, delta-like protein 1/preadipocyte factor-1, proliferating cell nuclear antigen, and QM/Jif-1. The Journal of Clinical Endocrinology and Metabolism 89, 2326–2337.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Strandberg Y, Gray C, Vuocolo T, Pickering L, Tellam RL (2005) Lipopolysaccharide and lipoteichoic acid induce different innate immune responses in bovine mammary epithelial cells. Cytokine 31, 72–86.
Crossref | PubMed |
open url image1

Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA , et al . (2004) A gene atlas of the mouse and human protein-encoding transcriptomes. Proceedings of the National Academy of Sciences of the United States of America 101, 6062–6067.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Takada S, Tevendale M, Baker J, Georgiades P, Campbell E, Freeman T, Johnson MH, Paulsen M, Ferguson-Smith AC (2000) Delta-like and Gtl2 are reciprocally expressed, differentially methylated linked imprinted genes on mouse chromosome 12. Current Biology 10, 1135–1138.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Tsibris JC, Segars J, Coppola D, Mane S, Wilbanks GD, O’Brien WF, Spellacy WN (2002) Insights from gene arrays on the development and growth regulation of uterine leiomyomata. Fertility and Sterility 78, 114–121.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

van Limpt V, Chan A, Caron H, Sluis PV, Boon K, Hermus MC, Versteeg R (2000) SAGE analysis of neuroblastoma reveals a high expression of the human homologue of the Drosophila Delta gene. Medical and Pediatric Oncology 35, 554–558.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Vuocolo T, Pearson R, Campbell P, Tellam RL (2003) Differential expression of Dlk-1 in bovine adipose tissue depots. Comparative Biochemistry and Physiology. B, Comparative Biochemistry 134, 315–333.
Crossref | GoogleScholarGoogle Scholar | open url image1

Wylie AA, Murphy SK, Orton TC, Jirtle RL (2000) Novel imprinted Dlk1/GTL2 domain on human chromosome 14 contains motifs that mimic those implicated in IGF2/H19 regulation. Genome Research 10, 1711–1718.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Yevtodiyenko A, Carr MS, Patel N, Schmidt JV (2002) Analysis of candidate imprinted genes linked to Dlk1-Gtl2 using a congenic mouse line. Mammalian Genome 13, 633–638.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Zhang X, Zhou Y, Mehta KR, Danila DC, Scolavino S, Johnson SR, Klibanski A (2003) A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells. The Journal of Clinical Endocrinology and Metabolism 88, 5119–5126.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Zhao J, Dahle D, Zhou Y, Klibanski A (2005) Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors. The Journal of Clinical Endocrinology and Metabolism 90, 2179–2186.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1