Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3.

Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3.
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DOI:
10.1038/s41467-021-23510-4
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发表时间:
2021-06-21
影响因子:
16.6
通讯作者:
Leeb M
Leeb M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Santini L;Halbritter F;Titz-Teixeira F;Suzuki T;Asami M;Ma X;Ramesmayer J;Lackner A;Warr N;Pauler F;Hippenmeyer S;Laue E;Farlik M;Bock C;Beyer A;Perry ACF;Leeb M

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在哺乳动物基因组中,差异甲基化区域(DMR)和组蛋白标记(包括组蛋白3赖氨酸27(H3K27me3)的三甲基化)在印迹基因上是不对称遗传的,以控制亲本偏向的基因表达。然而,无论是父母的起源特异性转录或印记已被全面映射在胚泡阶段的植入前发育。在这里,我们通过在小鼠植入前胚胎中整合转录组和表观基因组方法来解决这个问题。我们发现71个基因在胚泡中表现出先前未报道的亲本来源特异性表达(nBiX:新胚泡印迹表达)。nBiX基因的单亲表达在植入后不久消失。单个单亲囊胚的微型全基因组亚硫酸氢盐测序(µWGBS)检测到859个DMR。我们进一步发现,16%的nBiX基因与DMR相关,而大多数与亲代偏置的H3K27me3相关,这表明Polycomb介导的印记在囊胚中的作用。nBiX基因被聚类:五个簇包含至少一个已发表的印迹基因,五个簇仅包含nBiX基因。这些数据表明,早期发展经历了一个复杂的程序阶段特定的印记涉及不同层次的监管。在大多数哺乳动物中,印记基因包含在每个亲本基因组中不同的表观遗传标记,并控制它们的亲本来源特异性表达。在这里,作者绘制了小鼠植入前胚胎中的印记基因,发现囊胚中印记基因的表达主要依赖于Polycomb介导的H3K27me3相关基因沉默。
In mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped at the blastocyst stage of preimplantation development. Here, we address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos. We find that seventy-one genes exhibit previously unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expressed). Uniparental expression of nBiX genes disappears soon after implantation. Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts detects 859 DMRs. We further find that 16% of nBiX genes are associated with a DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered: five clusters contained at least one published imprinted gene, and five clusters exclusively contained nBiX genes. These data suggest that early development undergoes a complex program of stage-specific imprinting involving different tiers of regulation. In most mammals, imprinted genes contain epigenetic marks that differ in each parental genome and control their parent-of-origin-specific expression. Here, the authors map imprinted genes in mouse preimplantation embryos and find that imprinted gene expression in blastocysts is mainly dependent on Polycomb-mediated H3K27me3-associated gene silencing.
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发表时间: 2017-03
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Borensztein M;Syx L;Ancelin K;Diabangouaya P;Picard C;Liu T;Liang JB;Vassilev I;Galupa R;Servant N;Barillot E;Surani A;Chen CJ;Heard E
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发表时间: 2014-02-01
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DOI: 10.1101/gad.318675.118
发表时间: 2018-12-01
影响因子: 10.5
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