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Scientific Understanding of Consciousness |
Epigenetics in Human Embryos
Nature 511, 540–541 (31 July 2014) Epigenetics: Cellular memory erased in human embryos Wolf Reik & Gavin Kelsey Epigenetics Programme, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK, and at the Centre for Trophoblast Research, University of Cambridge [paraphrase] Epigenetic modifications are changes to the genome that can affect gene expression without altering DNA sequence. Like DNA itself, certain epigenetic modifications can be copied faithfully when cells divide, allowing daughter cells to retain this information from their parents. This ensures that gene expression is maintained in a stable manner down cell lineages. One such modification is methylation, whereby methyl groups are added to DNA. There is a massive loss of DNA methylation from most of the genome immediately after fertilization in human embryos. Thus, methylation memory is erased on a global scale — an epigenetic reprogramming step that seems to be fundamental in mammals. DNA methylation usually represses transcription, and primarily occurs on cytosine bases in the dinucleotide sequence cytosine–guanine (CpG, where p denotes the phosphate backbone of DNA, indicating that the nucleotides are on the same DNA strand). Because Watson–Crick base-pairing dictates that C pairs with G on complementary DNA strands, CpG sequences align and both strands are methylated in the same place. Therefore, methylation patterns can be passed on when cells divide, through the CpG 'memory module'. This inheritance of epigenetic information is vital in specialized cell lineages, which must maintain their identity as they divide — for example, dividing blood cells maintain their epigenetic identity to give rise to daughters that are also blood cells. Genome-wide analyses permit a detailed survey of distinct regions of DNA sequence whose function is known to be modified by methylation, allowing investigation of how they behave in the face of global demethylation. Such regions include 'imprinted' genes, CpG-rich genetic regions called CpG islands, and transposons (DNA sequences that can move about the genome). Imprinted genes are those that are expressed preferentially from one parental chromosome (maternal or paternal), unlike most genes, which can be expressed from both chromosomes. Unusually, epigenetic memory in imprinted sequences is retained throughout development. Researchers confirmed this in human embryos, which they found carried methylation memories from the embryos' parents in conserved imprinted regions. Transposons need to be treated with caution during reprogramming, because demethylation might cause their transcriptional activation. If they are evolutionarily 'young' and relatively unmutated, this might lead to their being able to move around in the genome, which could result in unwanted mutations. The new studies provide an atlas of methylation reprogramming in early human embryos and hence a foundation for studying epigenetic regulation of human development. This is vital if we are to understand the epigenetic mechanisms that control pluripotency and differentiation. [end of paraphrase]
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