受精直後の遺伝子活性は、胚がどのように形成されるかを推測するのに使われている。今、科学者たちは、がんも同じように始まるのではないかと考えています。 Gene activity immediately after fertilisation is used to infer how an embryo forms. Scientists now ask if cancer begins the same way.
2022-10-03 バース大学
このモデルは、受精に伴う無数の事象が相乗的に作用して、胚の遺伝子発現をスイッチすることを示唆している。
このモデルを拡張して、胚の形成を開始するスイッチは、がんも開始する可能性があると予測した。
分子生物学的に言えば、がんの起源がどのようなものなのかさえわかっていない。新しい胚をスタートさせるスイッチを理解することは、癌の導火線がどのように点灯するのかを明らかにするための実験プラットフォームとなる。
<関連情報>
- https://www.bath.ac.uk/announcements/do-human-embryos-and-cancer-share-the-same-starting-fuse/
- https://www.cell.com/trends/cell-biology/fulltext/S0962-8924(22)00211-2
哺乳類胚の転写の開始:始まりから始めること The initiation of mammalian embryonic transcription: to begin at the beginning
Anthony C.F. Perry,Maki Asami,Brian Y.H. Lam,Giles S.H. Yeo
Trends in Cell Biology Published:September 28, 2022
DOI:https://doi.org/10.1016/j.tcb.2022.08.008
Highlights
- Our high-resolution single-cell RNA-sequencing revealed that in human embryos, transcription initiates at the one-cell stage, earlier than widely thought.
- The new findings suggest that fertilization itself triggers transcription [embryonic genome activation (EGA)] by activating maternal transcription factors.
- EGA mostly utilizes canonical promoters and produces normatively spliced, protein-coding transcripts.
- The first genes expressed in the embryo predict upregulation by cancer-associated transcription factors, including MYC and MYCN, linking the onset of embryogenesis to cancer.
Gamete (sperm and oocyte) genomes are transcriptionally silent until embryonic genome activation (EGA) following fertilization. EGA in humans had been thought to occur around the eight-cell stage, but recent findings suggest that it is triggered in one-cell embryos, by fertilization. Phosphorylation and other post-translational modifications during fertilization may instate transcriptionally favorable chromatin and activate oocyte-derived transcription factors (TFs) to initiate EGA. Expressed genes lay on cancer-associated pathways and their identities predict upregulation by MYC and other cancer-associated TFs. One interpretation of this is that the onset of EGA, and the somatic cell trajectory to cancer, are mechanistically related: cancer initiates epigenetically. We describe how fertilization might be linked to the initiation of EGA and involve distinctive processes recapitulated in cancer.
