Conservation of the H19 noncoding RNA and H19-IGF2 imprinting mechanism in therians

被引：157

作者：

Smits, Guillaume ^{[1
]}

Mungall, Andrew J. ^{[2
]}

Griffiths-Jones, Sam ^{[3
]}

Smith, Paul ^{[1
]}

Beury, Delphine ^{[1
]}

Matthews, Lucy ^{[2
]}

Rogers, Jane ^{[2
]}

Pask, Andrew J. ^{[4
]}

Shaw, Geoff ^{[4
]}

VandeBerg, John L. ^{[5
]}

McCarrey, John R. ^{[6
]}

Renfree, Marilyn B. ^{[4
]}

Reik, Wolf ^{[1
]}

Dunham, Ian ^{[2
]}

机构：

[1] Babraham Inst, Lab Dev Genet & Imprinting, Cambridge CB22 3AT, England

[2] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

[3] Univ Manchester, Fac Life Sci, Manchester M13 9PL, England

[4] Univ Melbourne, Dept Zool, Victoria 3010, Australia

[5] SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78227 USA

[6] Univ Texas San Antonio, Dept Biol, San Antonio, TX 78249 USA

来源：

NATURE GENETICS | 2008年 / 40卷 / 08期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

D O I：

10.1038/ng.168

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Comparisons between eutherians and marsupials suggest limited conservation of the molecular mechanisms that control genomic imprinting in mammals. We have studied the evolution of the imprinted IGF2-H19 locus in therians. Although marsupial orthologs of protein-coding exons were easily identified, the use of evolutionarily conserved regions and low-stringency Bl2seq comparisons was required to delineate a candidate H19 noncoding RNA sequence. The therian H19 orthologs show miR-675 and exon structure conservation, suggesting functional selection on both features. Transcription start site sequences and poly(A) signals are also conserved. As in eutherians, marsupial H19 is maternally expressed and paternal methylation upstream of the gene originates in the male germline, encompasses a CTCF insulator, and spreads somatically into the H19 gene. The conservation in all therians of the mechanism controlling imprinting of the IGF2-H19 locus suggests a sequential model of imprinting evolution.

引用

页码：971 / 976

页数：6

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[1] Insulin is imprinted in the placenta of the marsupial, Macropus eugenii [J].