Genome-wide parent-of-origin DNA methylation analysis reveals the intricacies of human imprinting and suggests a germline methylation-independent mechanism of establishment

被引：273

作者：

Court, Franck ^{[1
]}

Tayama, Chiharu ^{[2
]}

Romanelli, Valeria ^{[1
]}

Martin-Trujillo, Alex ^{[1
]}

Iglesias-Platas, Isabel ^{[3
]}

Okamura, Kohji ^{[4
]}

Sugahara, Naoko ^{[2
]}

Simon, Carlos ^{[5
]}

Moore, Harry ^{[6
]}

Harness, Julie V. ^{[7
]}

Keirstead, Hans ^{[7
]}

Sanchez-Mut, Jose Vicente ^{[8
]}

Kaneki, Eisuke ^{[9
]}

Lapunzina, Pablo ^{[10
]}

Soejima, Hidenobu ^{[11
]}

Wake, Norio

Esteller, Manel ^{[12
,13
]}

Ogata, Tsutomu ^{[14
]}

Hata, Kenichiro

Nakabayashi, Kazuhiko ^{[2
]}

Monk, David ^{[1
]}

机构：

[1] Hosp Duran Reynals, Inst Invest Biomed Bellvitge, Canc Epigenet & Biol Program, Imprinting & Canc Grp, Barcelona 08908, Spain

[2] Natl Res Inst Child Hlth & Dev, Dept Maternal Fetal Biol, Tokyo 1578535, Japan

[3] Fundacio Sant Joan de Deu, Hosp Sant Joan de Deu, Serv Neonatol, Barcelona 08950, Spain

[4] Natl Res Inst Child Hlth & Dev, Dept Syst Biomed, Tokyo 1578535, Japan

[5] IVI Univ Valencia, INCLIVA, Fundacion IVI Inst Univ, Valencia 46980, Spain

[6] Univ Sheffield, Dept Biomed Sci, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England

[7] Univ Calif Irvine, Dept Anat & Neurobiol, Sch Med, Sue & Bill Gross Stem Cell Res Ctr,Reeve Irvine R, Placentia, CA 92670 USA

[8] Hosp Duran & Reynals, Inst Invest Biomed Bellvitge, Canc Epigenet & Biol Program, Canc Epigenet Grp, Barcelona 08908, Spain

[9] Kyushu Univ, Grad Sch Med Sci, Dept Obstet & Gynecol, Fukuoka 8128582, Japan

[10] Univ Autonoma Madrid, CIBERER, IDIPAZ Hosp Univ La Paz, Inst Genet Med & Mol, Madrid 28046, Spain

[11] Saga Univ, Fac Med, Dept Biomol Sci, Div Mol Genet & Epigenet, Saga 8498501, Japan

[12] Univ Barcelona, Sch Med, Dept Psychol Sci 2, Barcelona 08306, Catalonia, Spain

[13] ICREA, Barcelona 08010, Catalonia, Spain

[14] Hamamatsu Univ, Sch Med, Dept Pediat, Hamamatsu, Shizuoka 4313192, Japan

来源：

GENOME RESEARCH | 2014年 / 24卷 / 04期

关键词：

UNIPARENTAL DISOMY; CHROMATIN; DOMAIN; REGION; IDENTIFICATION; SEQUENCE; 5-METHYLCYTOSINE; INDIVIDUALS; MUTATIONS; PLACENTAS;

D O I：

10.1101/gr.164913.113

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Differential methylation between the two alleles of a gene has been observed in imprinted regions, where the methylation of one allele occurs on a parent-of-origin basis, the inactive X-chromosome in females, and at those loci whose methylation is driven by genetic variants. We have extensively characterized imprinted methylation in a substantial range of normal human tissues, reciprocal genome-wide uniparental disomies, and hydatidiform moles, using a combination of whole-genome bisulfite sequencing and high-density methylation microarrays. This approach allowed us to define methylation profiles at known imprinted domains at base-pair resolution, as well as to identify 21 novel loci harboring parent-of-origin methylation, 15 of which are restricted to the placenta. We observe that the extent of imprinted differentially methylated regions (DMRs) is extremely similar between tissues, with the exception of the placenta. This extra-embryonic tissue often adopts a different methylation profile compared to somatic tissues. Further, we profiled all imprinted DMRs in sperm and embryonic stem cells derived from parthenogenetically activated oocytes, individual blastomeres, and blastocysts, in order to identify primary DMRs and reveal the extent of reprogramming during preimplantation development. Intriguingly, we find that in contrast to ubiquitous imprints, the majority of placenta-specific imprinted DMRs are unmethylated in sperm and all human embryonic stem cells. Therefore, placental-specific imprinting provides evidence for an inheritable epigenetic state that is independent of DNA methylation and the existence of a novel imprinting mechanism at these loci.

引用

页码：554 / 569

页数：16

共 64 条

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