Methylomic trajectories across human fetal brain development.
Methylomic trajectories across human fetal brain development.
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DOI：
10.1101/gr.180273.114
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发表时间：
2015-03
期刊：
影响因子：
7
通讯作者：
Mill J
中科院分区：
文献类型：
--
作者：
Spiers H;Hannon E;Schalkwyk LC;Smith R;Wong CC;O'Donovan MC;Bray NJ;Mill J
表观遗传过程在发育过程中的转录调控中起着关键作用。围产期从头DNA甲基转移酶的动态表达以及与甲基-CpG结合蛋白2（MECP 2）基因突变相关的神经发育缺陷凸显了DNA甲基化在胎儿大脑发育中的重要性。然而，迄今为止，我们对胎儿大脑发育过程中表观基因组的时间变化的了解是有限的。我们在179个人类胎儿大脑样本（100名男性，79名女性）中量化了400，000个位点的全基因组DNA甲基化模式，时间跨度为受孕后23至184天。我们在>7%的位点上发现了胎儿脑发育过程中DNA甲基化的高度显著变化，随着胎儿年龄的增长，基因座的富集变得低甲基化。与胎儿大脑发育过程中DNA甲基化的发育变化相关的位点在启动子调控区中显著代表不足，但在CpG岛（海岸和货架）和基因体侧翼区域中显著代表过多。在男性和女性之间的一些常染色体位点观察到DNA甲基化的高度显着差异，少数区域显示出跨大脑发育的性别特异性DNA甲基化轨迹。加权基因commethylation网络分析（WGCNA）显示离散模块的commethylated基因座与胎儿年龄显着丰富的基因参与神经发育过程。据我们所知，这是迄今为止对人类胎儿大脑发育中DNA甲基化的最广泛的研究，证实了产前时期是一个相当大的表观基因组可塑性时期。
Epigenetic processes play a key role in orchestrating transcriptional regulation during development. The importance of DNA methylation in fetal brain development is highlighted by the dynamic expression of de novo DNA methyltransferases during the perinatal period and neurodevelopmental deficits associated with mutations in the methyl-CpG binding protein 2 (MECP2) gene. However, our knowledge about the temporal changes to the epigenome during fetal brain development has, to date, been limited. We quantified genome-wide patterns of DNA methylation at ∼400,000 sites in 179 human fetal brain samples (100 male, 79 female) spanning 23 to 184 d post-conception. We identified highly significant changes in DNA methylation across fetal brain development at >7% of sites, with an enrichment of loci becoming hypomethylated with fetal age. Sites associated with developmental changes in DNA methylation during fetal brain development were significantly underrepresented in promoter regulatory regions but significantly overrepresented in regions flanking CpG islands (shores and shelves) and gene bodies. Highly significant differences in DNA methylation were observed between males and females at a number of autosomal sites, with a small number of regions showing sex-specific DNA methylation trajectories across brain development. Weighted gene comethylation network analysis (WGCNA) revealed discrete modules of comethylated loci associated with fetal age that are significantly enriched for genes involved in neurodevelopmental processes. This is, to our knowledge, the most extensive study of DNA methylation across human fetal brain development to date, confirming the prenatal period as a time of considerable epigenomic plasticity.
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影响因子：
46.9
作者：
Ball, Madeleine P.;Li, Jin Billy;Gao, Yuan;Lee, Je-Hyuk;LeProust, Emily M.;Park, In-Hyun;Xie, Bin;Daley, George Q.;Church, George M.
通讯作者：
Church, George M.
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14.9
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Flicek P;Amode MR;Barrell D;Beal K;Billis K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fitzgerald S;Gil L;Girón CG;Gordon L;Hourlier T;Hunt S;Johnson N;Juettemann T;Kähäri AK;Keenan S;Kulesha E;Martin FJ;Maurel T;McLaren WM;Murphy DN;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ruffier M;Sheppard D;Taylor K;Thormann A;Trevanion SJ;Vullo A;Wilder SP;Wilson M;Zadissa A;Aken BL;Birney E;Cunningham F;Harrow J;Herrero J;Hubbard TJ;Kinsella R;Muffato M;Parker A;Spudich G;Yates A;Zerbino DR;Searle SM
通讯作者：
Searle SM
影响因子：
3.7
作者：
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通讯作者：
Carell T
影响因子：
2.7
作者：
Fujimoto, Motoaki;Takagi, Yasushi;Tanigaki, Kenji
通讯作者：
Tanigaki, Kenji
影响因子：
14.9
作者：
Basu SN;Kollu R;Banerjee-Basu S
通讯作者：
Banerjee-Basu S