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作者:Gregory Hannon 来源:《细胞》 发布时间:2011-9-21 # ^7 l6 I: @7 H
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来自冷泉港实验室,霍德华休斯医学院,南加州大学等处的研究人员分析比对了人类精子,黑猩猩精子,以及人类胚胎干细胞的胞嘧啶甲基化变化,从中发现了表观基因组学在进化中的影响,这些研究公布在Cell杂志封面。
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领导这项研究的是冷泉港实验室的Gregory J. Hannon教授,以及南加州大学的Andrew D. Smith教授,前者是小RNA研究领域的先驱,曾主编了冷泉港实验室技术手册:《MicroRNA研究方法》等,后者是甲基化研究领域的知名学者。
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在哺乳动物早期发育阶段,比如精细胞,和胚胎前植入阶段,细胞中的DNA会发生几乎完全的甲基化重洗牌,这对于发育阶段具有重要的意义。
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在这篇文章中,研究人员比对了人类精子,黑猩猩精子,以及人类胚胎干细胞的胞嘧啶甲基化变化,分析了这些甲基化发生的区域,从中发现虽然在胚胎干细胞和精子中,大部分启动子都逃避了甲基化,但是对应的低甲基化区域表现出了潜在的结构差异。比对人类和黑猩猩的甲基化情况,研究人员发现了一群差异甲基化启动子亚群,以及逆转录转座子亚群中的显著差异甲基化,这说明基因组序列中存在明显的这种进化影响。! t% \3 L( t0 j" Z9 O+ p* d
1 ]7 A: T1 u, A这项研究发现了决定男性精细胞和体细胞DNA甲基化模式差异的特征,以及这些特征元素在人类和黑猩猩中差别。
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表观基因组学是指在基因组的水平上研究表观遗传修饰的学科,表观基因组学使人们对基因组的认识又增加了一个新视点:对基因组而言,不仅仅是序列包含遗传信息,而且其修饰也可以记载遗传信息。
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欧洲的生物学家于1999年成立了“人类表观基因组联合研究体”。2004年欧洲还进一步成立“表观基因组学”先进研究网络,表观基因组学研究已渐入佳境。有关专家认为,过去教科书一直认为遗传的分子基础是核酸,生命的遗传信息储存在核酸的碱基序列上。随着表观基因组学的兴起和有关研究工作的全面进展,这种经典的遗传观念正面临着巨大的挑战。(来源:生物通 万纹)9 S' w' {( p1 n- j5 t, L
Sperm Methylation Profiles Reveal Features of Epigenetic Inheritance and Evolution in Primates7 x5 k( u- ^1 W6 o' ^8 i- k9 p
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Cell, Volume 146, Issue 6, 1029-1041, 16 September 2011
9 u- C4 L6 C: c- XCopyright 2011 Elsevier Inc. All rights reserved.
) y1 _5 r: q% u3 l$ H10.1016/j.cell.2011.08.016% g+ {0 a' S1 j C# D
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Referred to by: Directional DNA Methylation Changes and ...
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9 j' ~+ m7 |- Q' F2 l5 a. uAuthors! f3 b } n, A# ^$ a
Antoine Molaro, Emily Hodges, Fang Fang, Qiang Song, W. Richard McCombie, Gregory J. Hannon, Andrew D. SmithSee AffiliationsHint: Rollover Authors and Affiliations Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA$ D# E8 Z U7 t7 h& h* w
Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA
7 A2 A. t& Y- @ Corresponding author/ U3 t, I( X2 ?0 _- t8 r- p( J
These authors contributed equally to this workHighlights
" T- r' ]! |. J hSingle-nucleotide resolution methylomes of human and chimp sperm were produced
0 F" t; r+ V4 p( Z0 g. ]/ E" bES cell and sperm hypomethylated regions (HMRs) are structurally distinct
, ~; v; C8 D; N8 S9 uA large number of repeats evade de novo methylation exclusively in sperm
$ T2 ~' \$ k, m- @The developmental period spent methylated determines pressure for CpG depletion2 A/ \+ ?8 ?0 a( ^7 W/ y% h+ `

2 H9 ~% x7 \5 gSummary
. Q4 \+ k- ?. V. s- Q. dDuring germ cell and preimplantation development, mammalian cells undergo nearly complete reprogramming of DNA methylation patterns. We profiled the methylomes of human and chimp sperm as a basis for comparison to methylation patterns of ESCs. Although the majority of promoters escape methylation in both ESCs and sperm, the corresponding hypomethylated regions show substantial structural differences. Repeat elements are heavily methylated in both germ and somatic cells; however, retrotransposons from several subfamilies evade methylation more effectively during male germ cell development, whereas other subfamilies show the opposite trend. Comparing methylomes of human and chimp sperm revealed a subset of differentially methylated promoters and strikingly divergent methylation in retrotransposon subfamilies, with an evolutionary impact that is apparent in the underlying genomic sequence. Thus, the features that determine DNA methylation patterns differ between male germ cells and somatic cells, and elements of these features have diverged between humans and chimpanzees., E, o: ^. ? l1 m$ {; u4 f) w
9 h" {+ h1 J$ _6 chttp://www.cell.com/abstract/S0092-8674(11)00942-1
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