분자유전학실험실 (단국대학교 분자생물학과)



 이성욱 ( 2017-07-25 19:31:38 , Hit : 808
 A Novel Mammalian Genomic Imprinting Mechanism

http://www.genengnews.com/gen-news-highlights/a-novel-mammalian-genomic-imprinting-mechanism/81254679?utm_medium=newsletter&utm_source=GEN+Daily+News+Highlights&utm_content=02&utm_campaign=GEN+Daily+News+Highlights_20170720


GEN News Highlights
More »
July 19, 2017

Louisa Cockbill

For more than 20 years, DNA methylation has been the only known mechanism for regulating mammalian germline imprinting. Now, researchers at Harvard Medical School and Boston Children’s Hospital have identified a new mechanism for imprinting in mice. The findings highlight that histone H3 lysine 27 trimethylation (H3K27me3) modifications are able to silence unmethylated regions of DNA in mouse embryogenesis. Details of this work were published online today in Nature, in an article entitled “Maternal H3K27me3 Controls DNA Methylation-Independent Genomic Imprinting.”

The activation of imprinted genes triggered by removal of H3K27me3 from developing embryos was the key experiment in the study. Yi Zhang, Ph.D., investigator at Harvard Medical School, Boston Children's Hospital, and Howard Hughes Medical Institute, explained the conceptual advance that this has brought to the field: “Previous studies in mice linking H3K27me2 to imprinting are mostly on the traditionally DNA-methylation-dependent genes, thus our study is the first to reveal [a] DNA-methylation-independent imprinting mechanism.” A total of 76 potential candidate genes imprinted by H3K27me3 were identified, several of which are linked to placental development.

Loss-of-imprinting causes a variety of developmental disorders, but the potential to therapeutically intervene by turning epigenetic modifications on or off is an easier solution than fixing a mutated or missing gene. Dr. Zhang reflects on two of the putative genes imprinted by H3K27me3 in mice: “Currently, imprinting defects in mouse Gab1 and Sfmbt2 genes exhibit placental developmental defects. Whether this function is conserved in humans remains to be seen.”

The team used DNase I sequencing of maternal and paternal pronuclei to map imprinted regions in mouse zygotes and morula embryos and compared these with genome-wide methylation sequencing data. First author Azusa Inoue, Ph.D., said, "Much to our surprise, the imprinted genes we looked at lacked DNA methylation, which told us there must be another mechanism at play." H3K27me3 was found to coat imprinted regions lacking DNA methylation, but only in the maternal gametes, indicating maternal specificity in H3K27me3-mediated imprinting.

The genes associated with this novel form of imprinting were found using H3K27me3 chromatin immunoprecipitation sequencing (ChIP-seq) datasets that compared paternal allele sites that are devoid of DNA methylation but harbored maternal allele-specific H3K27me3. However, Zhang points out that, in contrast to DNA-methylated imprinting markers, “most of the H3K27me3-mediated imprinting is transient, and only a few are maintained in post-implantation embryos and placenta. We currently do not know why this imprinting is mostly transient and why some of them are maintained.”

Previous studies in mice had shown H3K27me3 present at DNA-methylated sites of imprinting, but the histone modification was not thought to be the causal factor in gene silencing. Although this was the first direct evidence of H3K27me3-mediated imprinting in mammals, there has been correlative evidence in marsupials, and Dr. Zhang acknowledges that the mechanism has been shown to be important in the grain plant maize.

The authors also noted that “since loss-of-imprinting of non-canonical imprinted genes is commonly observed in placentae of all cloned mouse embryos, it will be interesting to determine whether defective H3K27me3-mediated imprinting contributes to abnormal placental overgrowth of cloned animals.” This raises potential intrigue in the wider applications of embryonic development research, namely reproductive technologies.

Going forward, the Harvard group seeks to examine whether the new imprinting mechanism is conserved in humans, Zhang explains. “We are collaborating with an in vitro fertilization (IVF) center to analyze discarded human embryos to see whether the related genes are imprinted in humans.”







  A Novel Mammalian Genomic Imprinting Mechanism  이성욱 2017/07/25 808
1186   Mammalian Immunity: What’s RNAi Got to Do with It?  이성욱 2017/07/25 701
1185   CRISPR Structure Data Reveal How Cas Enzymes Choose Target  이성욱 2017/07/25 1084
1184   Anti-CRISPR Protein Reduces Off-Target Effects  이성욱 2017/07/14 788
1183   CRISPR Encodes Movie into Bacteria, Then DNA Sequencing Plays It  이성욱 2017/07/14 1017
1182   [바이오토픽] CRISPR를 이용하여 세균의 DNA에 영화를 저장!  이성욱 2017/07/14 860
1181   [바이오토픽] FDA 자문위원회, CAR-T(chimeric antigen receptor T cell) 승인 만장일치로 권고  이성욱 2017/07/14 744
1180   유전자치료제 '인보사' 연골재생 입증못해도 허가받은 까닭  이성욱 2017/07/14 741
1179   코오롱 인보사허가  이성욱 2017/07/12 700
1178   CRISPR Platform Scans DNA to Predict Off-Target Effects  이성욱 2017/07/02 1126
1177   Fixing CRISPR  이성욱 2017/06/27 1002
1176   [미국] 듀폰, 유전자가위 기술 적용 옥수수 출시를 위한 노력  이성욱 2017/06/22 907
1175   [바이오토픽] CRISPR를 역이용하는 파지(phage), 항생제내성 세균을 물리치는 신무기  이성욱 2017/06/22 1164
1174   [바이오 업계 소식: From Startups to Moguls] CRISPR-Cas9에 대한 경고와 업계 반응  이성욱 2017/06/14 695
1173   Was a Drop in CRISPR Firms’ Stock Warranted?  이성욱 2017/06/09 1206
1172   First In Vivo Human Genome Editing to Be Tested in New Clinical Trial  이성욱 2017/05/18 766
1171   독감바이러스의 ‘RNA 도둑질’  이성욱 2017/05/08 803
1170   More Tooth, More Tail in CRISPR Operations  이성욱 2017/04/25 900
1169   Gut Microbes Contribute to Age-Associated Inflammation in Mice  이성욱 2017/04/14 1392
1168   CRISPR Corrects Duchenne-Causing Mutations  이성욱 2017/04/14 839

[1][2][3][4] 5 [6][7][8][9][10]..[64] [다음 10개]
 

Copyright 1999-2021 Zeroboard / skin by ROBIN