DNMT1

DNMT1（DNA (cytosine-5)-methyltransferase 1）は、DNAメチル化の過程において、DNAの特定のCpG（英語版）構造へメチル基の転移を触媒する酵素である。ヒトでは、DNMT1遺伝子によってコードされる。DNMT1はDNAメチルトランスフェラーゼファミリーの一部を構成する。このファミリーには他にDNMT3AやDNMT3Bが含まれる。 この酵素はDNAの維持メチル化を担い、受け継がれたエピジェネティックなパターンの複製の正確性を保証している。ヘミメチル化DNA上のCpGのメチル化に対して非常に明確な選択性を有する。しかしながら、DNMT1はトランスポゾンや父親由来のインプリンティング制御領域など特定のゲノム条件下ではde novoメチル化も触媒する。メチル化パターンの異常は、ヒトの特定種の腫瘍や発生異常と関係している。 DNMT1は次に挙げる因子と相互作用することが示されている。 DMAP1（英語版） DNMT3A DNMT3B HDAC2（英語版） PCNA RB1 G9A（英語版） DNMT1は細胞周期のS期に高度に転写され、娘DNA鎖に新たに形成されたヘミメチル化部位のメチル化に必要である。PCNAやUHRF1（英語版）との相互作用は、DNMT1の複製フォークへの局在への関与が示唆されている。DNMT1とG9aの直接的な協働は、細胞分裂時のDNAとヒストンH3リジン9番残基（H3K9）のメチル化を調整している。このクロマチンのメチル化は、哺乳類の発生過程での遺伝子発現の安定的な抑制に必要である。 遺伝子ノックアウト実験からは、この酵素がマウス細胞におけるメチル化の大部分を担っていることが示されており、胚発生にも必要不可欠である。母性因子と接合子由来のDnmt1の双方の欠損によって、胚盤胞ではインプリンティング領域が完全に脱メチル化されることも示されている。 DNMT1は造血幹細胞（HSC）において重要な役割を果たす。DNMT1が減少したHSCは、移植後に効率的に自己複製を行うことができない。腸管上皮幹細胞（ISC）や乳腺幹細胞（MaSC）など他の種類の幹細胞でも重要であることが示されている。DNMT1の条件的欠失は、腸管のメチル化の全体的な低下と腸陰窩の拡大を引き起こし、ISCの分化のタイミングやMaSCの増殖と維持に変化が生じる。 ^ a b c GRCh38: Ensembl release 89: ENSG00000130816 - Ensembl, May 2017 ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000004099 - Ensembl, May 2017 ^ Human PubMed Reference: ^ Mouse PubMed Reference: ^ “Isolation and characterization of the cDNA encoding human DNA methyltransferase”. 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