Genome Research

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wylie, A. A.
Right arrow Articles by Jirtle, R. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wylie, A. A.
Right arrow Articles by Jirtle, R. L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Vol. 10, Issue 11, 1711-1718, November 2000

LETTER
Novel Imprinted DLK1/GTL2 Domain on Human Chromosome 14 Contains Motifs that Mimic Those Implicated in IGF2/H19 Regulation

Andrew A. Wylie,1,2 Susan K. Murphy,1 Terry C. Orton,2 and Randy L. Jirtle1,3

1 Departments of Radiation Oncology and Pathology, Duke University Medical Center, Durham, NC 27710, USA; 2 Safety Assessment, AstraZeneca Pharmaceuticals, Alderley Edge, SK1 04TG, UK

The evolution of genomic imprinting in mammals occurred more than 100 million years ago, and resulted in the formation of genes that are functionally haploid because of parent-of-origin-dependent expression. Despite ample evidence from studies in a number of species suggesting the presence of imprinted genes on human chromosome 14, their identity has remained elusive. Here we report the identification of two reciprocally imprinted genes, GTL2 and DLK1, which together define a novel imprinting cluster on human chromosome 14q32. The maternally expressed GTL2 (gene trap locus 2) gene encodes for a nontranslated RNA. DLK1 (delta, Drosophila, homolog-like 1) is a paternally expressed gene that encodes for a transmembrane protein containing six epidermal growth factor (EGF) repeat motifs closely related to those present in the delta/notch/serrate family of signaling molecules. The paternal expression, chromosomal localization, and biological function of DLK1 also make it a likely candidate gene for the callipyge phenotype in sheep. Many of the predicted structural and regulatory features of the DLK1/GTL2 domain are highly analogous to those implicated in IGF2/H19 imprint regulation, including two hemimethylated consensus binding sites for the vertebrate enhancer blocking protein, CTCF. These results provide evidence that a common mechanism and domain organization may be used for juxtapositioned, reciprocally imprinted genes.

3 Corresponding author.

10:1711-1718 ©2000 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/00 $5.00
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Stem CellsHome page
L. C. Laurent, J. Chen, I. Ulitsky, F.-J. Mueller, C. Lu, R. Shamir, J.-B. Fan, and J. F. Loring
Comprehensive MicroRNA Profiling Reveals a Unique Human Embryonic Stem Cell Signature Dominated by a Single Seed Sequence
Stem Cells, June 1, 2008; 26(6): 1506 - 1516.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
S. Renaud, E. M. Pugacheva, M. D. Delgado, R. Braunschweig, Z. Abdullaev, D. Loukinov, J. Benhattar, and V. Lobanenkov
Expression of the CTCF-paralogous cancer-testis gene, brother of the regulator of imprinted sites (BORIS), is regulated by three alternative promoters modulated by CpG methylation and by CTCF and p53 transcription factors
Nucleic Acids Res., December 18, 2007; 35(21): 7372 - 7388.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
I K Temple, V Shrubb, M Lever, H Bullman, and D J G Mackay
Isolated imprinting mutation of the DLK1/GTL2 locus associated with a clinical presentation of maternal uniparental disomy of chromosome 14
J. Med. Genet., October 1, 2007; 44(10): 637 - 640.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Zhou, Y. Zhong, Y. Wang, X. Zhang, D. L. Batista, R. Gejman, P. J. Ansell, J. Zhao, C. Weng, and A. Klibanski
Activation of p53 by MEG3 Non-coding RNA
J. Biol. Chem., August 24, 2007; 282(34): 24731 - 24742.
[Abstract] [Full Text] [PDF]

Home page
 J Child NeurolHome page
M. Tzoufi, C. Kanioglou, A. Dasoula, I. Asproudis, A. Tsatsoulis, C. Sismani, P. C. Patsalis, I. Georgiou, and M. Syrrou
Mosaic Trisomy r(14) Associated With Epilepsy and Mental Retardation
J Child Neurol, July 1, 2007; 22(7): 869 - 873.
[Abstract] [PDF]

Home page
 Physiol. Rev.Home page
M. F. Mehler and J. S. Mattick
Noncoding RNAs and RNA Editing in Brain Development, Functional Diversification, and Neurological Disease
Physiol Rev, July 1, 2007; 87(3): 799 - 823.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
J. Huang, X. Zhang, M. Zhang, J.-D. Zhu, Y.-L. Zhang, Y. Lin, K.-S. Wang, X.-F. Qi, Q. Zhang, G.-Z. Liu, et al.
Up-regulation of DLK1 as an imprinted gene could contribute to human hepatocellular carcinoma
Carcinogenesis, May 1, 2007; 28(5): 1094 - 1103.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
K.-A. Kim, J.-H. Kim, Y. Wang, and H. S. Sul
Pref-1 (Preadipocyte Factor 1) Activates the MEK/Extracellular Signal-Regulated Kinase Pathway To Inhibit Adipocyte Differentiation
Mol. Cell. Biol., March 15, 2007; 27(6): 2294 - 2308.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
T. Vuocolo, K. Byrne, J. White, S. McWilliam, A. Reverter, N. E. Cockett, and R. L. Tellam
Identification of a gene network contributing to hypertrophy in callipyge skeletal muscle
Physiol Genomics, February 12, 2007; 28(3): 253 - 272.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
Y. Wang, K.-A. Kim, J.-H. Kim, and H. S. Sul
Pref-1, a Preadipocyte Secreted Factor That Inhibits Adipogenesis
J. Nutr., December 1, 2006; 136(12): 2953 - 2956.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
D. Mainieri, S. Summermatter, J. Seydoux, J.-P. Montani, S. Rusconi, A. P. Russell, O. Boss, A. J. Buchala, and A. G. Dulloo
A role for skeletal muscle stearoyl-CoA desaturase 1 in control of thermogenesis
FASEB J, August 1, 2006; 20(10): 1751 - 1753.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. Wang and H. S. Sul
Ectodomain Shedding of Preadipocyte Factor 1 (Pref-1) by Tumor Necrosis Factor Alpha Converting Enzyme (TACE) and Inhibition of Adipocyte Differentiation.
Mol. Cell. Biol., July 1, 2006; 26(14): 5421 - 5435.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
S. K. Murphy, Z. Huang, Y. Wen, M. A. Spillman, R. S. Whitaker, L. R. Simel, T. D. Nichols, J. R. Marks, and A. Berchuck
Frequent IGF2/H19 Domain Epigenetic Alterations and Elevated IGF2 Expression in Epithelial Ovarian Cancer
Mol. Cancer Res., April 1, 2006; 4(4): 283 - 292.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
T. Kawakami, T. Chano, K. Minami, H. Okabe, Y. Okada, and K. Okamoto
Imprinted DLK1 is a putative tumor suppressor gene and inactivated by epimutation at the region upstream of GTL2 in human renal cell carcinoma
Hum. Mol. Genet., March 15, 2006; 15(6): 821 - 830.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
H. K. Evans, J. R. Weidman, D. O. Cowley, and R. L. Jirtle
Comparative Phylogenetic Analysis of Blcap/Nnat Reveals Eutherian-Specific Imprinted Gene
Mol. Biol. Evol., August 1, 2005; 22(8): 1740 - 1748.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. D. Choi, L. A. Underkoffler, A. J. Wood, J. N. Collins, P. T. Williams, J. A. Golden, E. F. Schuster Jr., K. M. Loomes, and R. J. Oakey
A Novel Variant of Inpp5f Is Imprinted in Brain, and Its Expression Is Correlated with Differential Methylation of an Internal CpG Island
Mol. Cell. Biol., July 1, 2005; 25(13): 5514 - 5522.
[Abstract] [Full Text] [PDF]

Home page
 Genome Res.Home page
P. P. Luedi, A. J. Hartemink, and R. L. Jirtle
Genome-wide prediction of imprinted murine genes
Genome Res., June 1, 2005; 15(6): 875 - 884.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. Zhao, D. Dahle, Y. Zhou, X. Zhang, and A. Klibanski
Hypermethylation of the Promoter Region Is Associated with the Loss of MEG3 Gene Expression in Human Pituitary Tumors
J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2179 - 2186.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
R Fukuzawa, R W Heathcott, I M Morison, and A E Reeve
Imprinting, expression, and localisation of DLK1 in Wilms tumours
J. Clin. Pathol., February 1, 2005; 58(2): 145 - 150.
[Abstract] [Full Text] [PDF]

Home page
 Genome Res.Home page
J. R. Weidman, S. K. Murphy, C. M. Nolan, F. S. Dietrich, and R. L. Jirtle
Phylogenetic Footprint Analysis of IGF2 in Extant Mammals
Genome Res., September 1, 2004; 14(9): 1726 - 1732.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
X. Zhang, Y. Zhou, K. R. Mehta, D. C. Danila, S. Scolavino, S. R. Johnson, and A. Klibanski
A Pituitary-Derived MEG3 Isoform Functions as a Growth Suppressor in Tumor Cells
J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5119 - 5126.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. Coombes, P. Arnaud, E. Gordon, W. Dean, E. A. Coar, C. M. Williamson, R. Feil, J. Peters, and G. Kelsey
Epigenetic Properties and Identification of an Imprint Mark in the Nesp-Gnasxl Domain of the Mouse Gnas Imprinted Locus
Mol. Cell. Biol., August 15, 2003; 23(16): 5475 - 5488.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
P. Arnaud, D. Monk, M. Hitchins, E. Gordon, W. Dean, C. V. Beechey, J. Peters, W. Craigen, M. Preece, P. Stanier, et al.
Conserved methylation imprints in the human and mouse GRB10 genes with divergent allelic expression suggests differential reading of the same mark
Hum. Mol. Genet., May 1, 2003; 12(9): 1005 - 1019.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
L G Dietz, A A Wylie, K A Rauen, S K Murphy, R L Jirtle, and P D Cotter
Exclusion of maternal uniparental disomy of chromosome 14 in patients referred for Prader-Willi syndrome using a multiplex methylation polymerase chain reaction assay
J. Med. Genet., April 1, 2003; 40(4): e46 - 46.
[Full Text] [PDF]

Home page
 GeneticsHome page
K. A. Maggert and K. G. Golic
The Y Chromosome of Drosophila melanogaster Exhibits Chromosome-Wide Imprinting
Genetics, November 1, 2002; 162(3): 1245 - 1258.
[Abstract] [Full Text] [PDF]

Home page
 Genome Res.Home page
B. A. Freking, S. K. Murphy, A. A. Wylie, S. J. Rhodes, J. W. Keele, K. A. Leymaster, R. L. Jirtle, and T. P.L. Smith
Identification of the Single Base Change Causing the Callipyge Muscle Hypertrophy Phenotype, the Only Known Example of Polar Overdominance in Mammals
Genome Res., October 1, 2002; 12(10): 1496 - 1506.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. S. Moon, C. M. Smas, K. Lee, J. A. Villena, K.-H. Kim, E. J. Yun, and H. S. Sul
Mice Lacking Paternally Expressed Pref-1/Dlk1 Display Growth Retardation and Accelerated Adiposity
Mol. Cell. Biol., August 1, 2002; 22(15): 5585 - 5592.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. Cavaille, H. Seitz, M. Paulsen, A. C. Ferguson-Smith, and J.-P. Bachellerie
Identification of tandemly-repeated C/D snoRNA genes at the imprinted human 14q32 domain reminiscent of those at the Prader-Willi/Angelman syndrome region
Hum. Mol. Genet., June 15, 2002; 11(13): 1527 - 1538.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. L. Thorvaldsen, M. R. W. Mann, O. Nwoko, K. L. Duran, and M. S. Bartolomei
Analysis of Sequence Upstream of the Endogenous H19 Gene Reveals Elements Both Essential and Dispensable for Imprinting
Mol. Cell. Biol., April 15, 2002; 22(8): 2450 - 2462.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
D Kamnasaran and D W Cox
Current status of human chromosome 14
J. Med. Genet., February 1, 2002; 39(2): 81 - 90.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. Takada, M. Paulsen, M. Tevendale, C.-E. Tsai, G. Kelsey, B. M. Cattanach, and A. C. Ferguson-Smith
Epigenetic analysis of the Dlk1-Gtl2 imprinted domain on mouse chromosome 12: implications for imprinting control from comparison with Igf2-H19
Hum. Mol. Genet., January 1, 2002; 11(1): 77 - 86.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
N. E. COCKETT, T. L. SHAY, and M. SMIT
Analysis of the sheep genome
Physiol Genomics, December 21, 2001; 7(2): 69 - 78.
[Abstract] [Full Text] [PDF]

Home page
 Genome Res.Home page
M. Paulsen, S. Takada, N. A. Youngson, M. Benchaib, C. Charlier, K. Segers, M. Georges, and A. C. Ferguson-Smith
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 Res., December 1, 2001; 11(12): 2085 - 2094.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
L. S. Weinstein, S. Yu, D. R. Warner, and J. Liu
Endocrine Manifestations of Stimulatory G Protein {alpha}-Subunit Mutations and the Role of Genomic Imprinting
Endocr. Rev., October 1, 2001; 22(5): 675 - 705.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
A. C. Ferguson-Smith and M. A. Surani
Imprinting and the Epigenetic Asymmetry Between Parental Genomes
Science, August 10, 2001; 293(5532): 1086 - 1089.
[Abstract] [Full Text] [PDF]

Home page
 Genome Res.Home page
C. Charlier, K. Segers, D. Wagenaar, L. Karim, S. Berghmans, O. Jaillon, T. Shay, J. Weissenbach, N. Cockett, G. Gyapay, et al.
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, antiPEG11, and MEG8
Genome Res., May 1, 2001; 11(5): 850 - 862.
[Abstract] [Full Text]

Home page
 Genome Res.Home page
T. H. Vu and A. R. Hoffman
Comparative Genomics Sheds Light on Mechanisms of Genomic Imprinting
Genome Res., November 1, 2000; 10(11): 1660 - 1663.
[Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Genes Dev. Learn. Mem.
Protein Science RNA Genome Res.