Species-Specific 5 mC and 5 hmC Genomic Landscapes Indicate Epigenetic Contribution to Human Brain Evolution.
Species-Specific 5 mC and 5 hmC Genomic Landscapes Indicate Epigenetic Contribution to Human Brain Evolution.
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DOI：
10.3389/fnmol.2018.00039
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发表时间：
2018
影响因子：
4.8
通讯作者：
Alisch RS
中科院分区：
文献类型：
--
作者：
Madrid A;Chopra P;Alisch RS
人类从非人灵长类进化而来，中枢神经系统发生了实质性变化，人类大脑进化的分子机制在很大程度上仍不清楚。胞嘧啶第五碳(5-甲基胞嘧啶；5 mC)的甲基化是与神经发育和神经系统疾病相关的重要表观遗传标记。在大脑中丰富的另一种修饰形式的胞嘧啶(5-羟甲基胞嘧啶；5-HMC)的出现进一步证实了这些表观遗传标记在神经发育中的作用，但人们对这些标记在大脑发育中的进化重要性知之甚少。在这里，人类和猴子的脑组织进行了分析，分别识别了5516个和4070个在物种之间差异甲基化和羟甲基化的基因座。对人类基因组的这些基因座的注释揭示了对神经系统发育至关重要的基因，这些基因与智力和更高的认知功能有关，如RELN和GNAS。此外，对这些差异甲基化和羟甲基化基因的本体论分析显示，神经元/免疫相关过程显著丰富，包括神经发生和轴突发育。最后，差异甲基化/羟甲基化位点两侧的序列含有显著丰富的神经发育重要转录因子(例如OTX1和PITX1)的结合位点，表明DNA甲基化可能通过介导转录因子与这些转录因子的结合来调节基因的表达。总而言之，这些数据支持在非人类灵长类动物的人脑进化和发育中动态的物种特定的表观遗传学贡献。
Human evolution from non-human primates has seen substantial change in the central nervous system, with the molecular mechanisms underlying human brain evolution remaining largely unknown. Methylation of cytosine at the fifth carbon (5-methylcytosine; 5 mC) is an essential epigenetic mark linked to neurodevelopment, as well as neurological disease. The emergence of another modified form of cytosine (5-hydroxymethylcytosine; 5 hmC) that is enriched in the brain further substantiates a role for these epigenetic marks in neurodevelopment, yet little is known about the evolutionary importance of these marks in brain development. Here, human and monkey brain tissue were profiled, identifying 5,516 and 4,070 loci that were differentially methylated and hydroxymethylated, respectively, between the species. Annotation of these loci to the human genome revealed genes critical for the development of the nervous system and that are associated with intelligence and higher cognitive functioning, such as RELN and GNAS. Moreover, ontological analyses of these differentially methylated and hydroxymethylated genes revealed a significant enrichment of neuronal/immunological–related processes, including neurogenesis and axon development. Finally, the sequences flanking the differentially methylated/hydroxymethylated loci contained a significant enrichment of binding sites for neurodevelopmentally important transcription factors (e.g., OTX1 and PITX1), suggesting that DNA methylation may regulate gene expression by mediating transcription factor binding on these transcripts. Together, these data support dynamic species-specific epigenetic contributions in the evolution and development of the human brain from non-human primates.
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影响因子：
14.9
作者：
Long HK;King HW;Patient RK;Odom DT;Klose RJ
通讯作者：
Klose RJ
DOI：
10.1073/pnas.93.24.13453
发表时间：
1996-11-26
影响因子：
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影响因子：
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作者：
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