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1
Domain regulation of imprinting cluster in Kip2/Lit1 subdomain on mouse chromosome 7F4/F5: large-scale DNA methylation analysis reveals that DMR-Lit1 is a putative imprinting control region.小鼠7F4/F5染色体上Kip2/Lit1亚结构域中印迹簇的结构域调控：大规模DNA甲基化分析表明DMR-Lit1是一个假定的印迹控制区域。
Genome Res. 2002 Dec;12(12):1860-70. doi: 10.1101/gr.110702.
2
Silencing of imprinted CDKN1C gene expression is associated with loss of CpG and histone H3 lysine 9 methylation at DMR-LIT1 in esophageal cancer.印记基因CDKN1C表达的沉默与食管癌中DMR-LIT1处CpG和组蛋白H3赖氨酸9甲基化的缺失有关。
Oncogene. 2004 May 27;23(25):4380-8. doi: 10.1038/sj.onc.1207576.
3
Loss of CpG methylation is strongly correlated with loss of histone H3 lysine 9 methylation at DMR-LIT1 in patients with Beckwith-Wiedemann syndrome.在贝克威思-维德曼综合征患者中，CpG甲基化的缺失与DMR-LIT1处组蛋白H3赖氨酸9甲基化的缺失密切相关。
Am J Hum Genet. 2003 Oct;73(4):948-56. doi: 10.1086/378595. Epub 2003 Aug 29.
4
Targeted disruption of the human LIT1 locus defines a putative imprinting control element playing an essential role in Beckwith-Wiedemann syndrome.对人类LIT1基因座的靶向破坏确定了一个假定的印记控制元件，该元件在贝克威思-维德曼综合征中起关键作用。
Hum Mol Genet. 2000 Sep 1;9(14):2075-83. doi: 10.1093/hmg/9.14.2075.
5
ZAC, LIT1 (KCNQ1OT1) and p57KIP2 (CDKN1C) are in an imprinted gene network that may play a role in Beckwith-Wiedemann syndrome.ZAC、LIT1（KCNQ1OT1）和p57KIP2（CDKN1C）处于一个可能在贝克威思-维德曼综合征中起作用的印记基因网络中。
Nucleic Acids Res. 2005 May 11;33(8):2650-60. doi: 10.1093/nar/gki555. Print 2005.
6
Domain regulation of imprinting cluster in Kip2/Lit1 subdomain on mouse chromosome 7F4/F5: large-scale DNA methylation analysis reveals that DMR-Lit1 is a putative imprinting control region.小鼠7F4/F5染色体上Kip2/Lit1亚结构域中印迹簇的结构域调控：大规模DNA甲基化分析表明DMR-Lit1是一个假定的印迹控制区域。
Genome Res. 2004 Sep;14(9):1820.
7
Multiple mechanisms regulate imprinting of the mouse distal chromosome 7 gene cluster.多种机制调控小鼠7号染色体远端基因簇的印记。
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8
Sequence-based structural features between Kvlqt1 and Tapa1 on mouse chromosome 7F4/F5 corresponding to the Beckwith-Wiedemann syndrome region on human 11p15.5: long-stretches of unusually well conserved intronic sequences of kvlqt1 between mouse and human.小鼠7F4/F5染色体上与人类11p15.5上的贝克威思-维德曼综合征区域相对应的Kvlqt1和Tapa1之间基于序列的结构特征：小鼠和人类之间kvlqt1内含子序列异常保守的长片段。
DNA Res. 2000 Jun 30;7(3):195-206. doi: 10.1093/dnares/7.3.195.
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The testis-specific factor CTCFL cooperates with the protein methyltransferase PRMT7 in H19 imprinting control region methylation.睾丸特异性因子CTCFL与蛋白质甲基转移酶PRMT7协同作用于H19印记控制区的甲基化。
PLoS Biol. 2006 Oct;4(11):e355. doi: 10.1371/journal.pbio.0040355.
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Syntenic organization of the mouse distal chromosome 7 imprinting cluster and the Beckwith-Wiedemann syndrome region in chromosome 11p15.5.小鼠7号染色体远端印记簇与11号染色体p15.5区域贝克威思-维德曼综合征区域的同线性组织。
Hum Mol Genet. 1998 Jul;7(7):1149-59. doi: 10.1093/hmg/7.7.1149.

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Methylation is maintained specifically at imprinting control regions but not other DMRs associated with imprinted genes in mice bearing a mutation in the intrinsically disordered domain.在具有内在无序结构域突变的小鼠中，甲基化特异性地维持在印记控制区域，而不是与印记基因相关的其他差异甲基化区域。
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2
Drug-induced loss of imprinting revealed using bioluminescent reporters of Cdkn1c.利用 Cdkn1c 的生物发光报告基因揭示药物诱导的印迹丢失
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5
Hemimethylation of CpG dyads is characteristic of secondary DMRs associated with imprinted loci and correlates with 5-hydroxymethylcytosine at paternally methylated sequences.CpG 二联体的半甲基化是与印迹基因座相关的二级 DMR 的特征，并且与父系甲基化序列中的 5-羟甲基胞嘧啶相关。
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Transcription factor ASCL2 is required for development of the glycogen trophoblast cell lineage.转录因子 ASCL2 是糖原滋养细胞谱系发育所必需的。
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Asymmetric DNA methylation of CpG dyads is a feature of secondary DMRs associated with the / imprinting cluster in mouse.CpG 二联体的不对称 DNA 甲基化是与小鼠 / 印记簇相关的次级差异甲基化区域的一个特征。
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Epigenetic Characterization of CDKN1C in Placenta Samples from Non-syndromic Intrauterine Growth Restriction.非综合征性宫内生长受限胎盘样本中CDKN1C的表观遗传学特征
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9
Genomic imprinting in mammals.哺乳动物中的基因组印记
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The Kcnq1ot1 long non-coding RNA affects chromatin conformation and expression of Kcnq1, but does not regulate its imprinting in the developing heart.Kcnq1ot1 长链非编码 RNA 影响染色质构象和 Kcnq1 的表达，但不调节其在发育心脏中的印记。
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本文引用的文献

1
A differentially methylated imprinting control region within the Kcnq1 locus harbors a methylation-sensitive chromatin insulator.Kcnq1基因座内一个差异甲基化的印记控制区域含有一个甲基化敏感的染色质绝缘子。
J Biol Chem. 2002 May 17;277(20):18106-10. doi: 10.1074/jbc.M200031200. Epub 2002 Mar 4.
2
Dnmt3L and the establishment of maternal genomic imprints.DNA甲基转移酶3L与母源基因组印记的建立
Science. 2001 Dec 21;294(5551):2536-9. doi: 10.1126/science.1065848. Epub 2001 Nov 22.
3
Disruption of an imprinted gene cluster by a targeted chromosomal translocation in mice.小鼠中靶向染色体易位对一个印记基因簇的破坏。
Nat Genet. 2001 Sep;29(1):78-82. doi: 10.1038/ng715.
4
Imprinting and the epigenetic asymmetry between parental genomes.印记与亲代基因组之间的表观遗传不对称性。
Science. 2001 Aug 10;293(5532):1086-9. doi: 10.1126/science.1064020.
5
Distant cis-elements regulate imprinted expression of the mouse p57( Kip2) (Cdkn1c) gene: implications for the human disorder, Beckwith--Wiedemann syndrome.远距离顺式元件调控小鼠p57（Kip2）（Cdkn1c）基因的印记表达：对人类疾病贝克威思-维德曼综合征的启示。
Hum Mol Genet. 2001 Jul 15;10(15):1601-9. doi: 10.1093/hmg/10.15.1601.
6
Establishment and maintenance of DNA methylation patterns in mouse Ndn: implications for maintenance of imprinting in target genes of the imprinting center.小鼠Ndn中DNA甲基化模式的建立与维持：对印记中心靶基因印记维持的影响
Mol Cell Biol. 2001 Apr;21(7):2384-92. doi: 10.1128/MCB.21.7.2384-2392.2001.
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Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer.癌症中DNA甲基化、染色质形成和基因表达的异常模式。
Hum Mol Genet. 2001 Apr;10(7):687-92. doi: 10.1093/hmg/10.7.687.
8
X-chromosome inactivation: counting, choice and initiation.X染色体失活：计数、选择与起始
Nat Rev Genet. 2001 Jan;2(1):59-67. doi: 10.1038/35047580.
9
Genomic imprinting: parental influence on the genome.基因组印记：亲本对基因组的影响。
Nat Rev Genet. 2001 Jan;2(1):21-32. doi: 10.1038/35047554.
10
Sequence and comparative analysis of the mouse 1-megabase region orthologous to the human 11p15 imprinted domain.与人类11p15印记域直系同源的小鼠1兆碱基区域的序列及比较分析。
Genome Res. 2000 Nov;10(11):1697-710. doi: 10.1101/gr.161800.

小鼠7F4/F5染色体上Kip2/Lit1亚结构域中印迹簇的结构域调控：大规模DNA甲基化分析表明DMR-Lit1是一个假定的印迹控制区域。

Domain regulation of imprinting cluster in Kip2/Lit1 subdomain on mouse chromosome 7F4/F5: large-scale DNA methylation analysis reveals that DMR-Lit1 is a putative imprinting control region.

作者信息

Yatsuki Hitomi, Joh Keiichiro, Higashimoto Ken, Soejima Hidenobu, Arai Yuji, Wang Youdong, Hatada Izuho, Obata Yayoi, Morisaki Hiroko, Zhang Zhongming, Nakagawachi Tetsuji, Satoh Yuji, Mukai Tsunehiro

机构信息

Department of Biochemistry, Saga Medical School, Saga, Saga 849-8501, Japan.

出版信息

Genome Res. 2002 Dec;12(12):1860-70. doi: 10.1101/gr.110702.

DOI:10.1101/gr.110702
PMID:12466290
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC187562/
Abstract

Mouse chromosome 7F4/F5, where the imprinting domain is located, is syntenic to human 11p15.5, the locus for Beckwith-Wiedemann syndrome. The domain is thought to consist of the two subdomains Kip2 (p57(kip2))/Lit1 and Igf2/H19. Because DNA methylation is believed to be a key factor in genomic imprinting, we performed large-scale DNA methylation analysis to identify the cis-element crucial for the regulation of the Kip2/Lit1 subdomain. Ten CpG islands (CGIs) were found, and these were located at the promoter sites, upstream of genes, and within intergenic regions. Bisulphite sequencing revealed that CGIs 4, 5, 8, and 10 were differentially methylated regions (DMRs). CGIs 4, 5, and 10 were methylated paternally in somatic tissues but not in germ cells. CGI8 was methylated in oocyte and maternally in somatic tissues during development. Parental-specific DNase I hypersensitive sites (HSSs) were found near CGI8. These data indicate that CGI8, called DMR-Lit1, is not only the region for gametic methylation but might also be the imprinting control region (ICR) of the subdomain.

摘要

印记域所在的小鼠7F4/F5染色体区域与人类11p15.5区域同线，后者是贝克威思-维德曼综合征的基因座。该区域被认为由Kip2（p57(kip2)）/Lit1和Igf2/H19这两个亚域组成。由于DNA甲基化被认为是基因组印记的关键因素，我们进行了大规模的DNA甲基化分析，以确定对Kip2/Lit1亚域调控至关重要的顺式元件。发现了10个CpG岛（CGIs），它们位于启动子位点、基因上游和基因间区域。亚硫酸氢盐测序显示，CGIs 4、5、8和10是差异甲基化区域（DMRs）。CGIs 4、5和10在体细胞组织中父本甲基化，但在生殖细胞中未甲基化。CGI8在发育过程中的卵母细胞中甲基化，在体细胞组织中母本甲基化。在CGI8附近发现了亲本特异性的DNase I超敏位点（HSSs）。这些数据表明，被称为DMR-Lit1的CGI8不仅是配子甲基化的区域，也可能是该亚域的印记控制区域（ICR）。