MacArthur Ian C, Dawlaty Meelad M
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, United States.
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, United States.
Front Cell Dev Biol. 2021 Feb 18;9:645335. doi: 10.3389/fcell.2021.645335. eCollection 2021.
Studies of tissue-specific epigenomes have revealed 5-hydroxymethylcytosine (5hmC) to be a highly enriched and dynamic DNA modification in the metazoan nervous system, inspiring interest in the function of this epigenetic mark in neurodevelopment and brain function. 5hmC is generated by oxidation of 5-methylcytosine (5mC), a process catalyzed by the ten-eleven translocation (TET) enzymes. 5hmC serves not only as an intermediate in DNA demethylation but also as a stable epigenetic mark. Here, we review the known functions of 5hmC and TET enzymes in neural progenitor cell biology and embryonic and postnatal neurogenesis. We also discuss how TET enzymes and 5hmC regulate neuronal activity and brain function and highlight their implications in human neurodevelopmental and neurodegenerative disorders. Finally, we present outstanding questions in the field and envision new research directions into the roles of 5hmC and TET enzymes in neurodevelopment.
对组织特异性表观基因组的研究表明，5-羟甲基胞嘧啶（5hmC）是后生动物神经系统中高度富集且动态变化的DNA修饰，这激发了人们对这种表观遗传标记在神经发育和脑功能中作用的兴趣。5hmC由5-甲基胞嘧啶（5mC）氧化产生，该过程由双加氧酶（TET）催化。5hmC不仅作为DNA去甲基化的中间体，还作为一种稳定的表观遗传标记。在这里，我们综述了5hmC和TET酶在神经祖细胞生物学以及胚胎期和出生后神经发生中的已知功能。我们还讨论了TET酶和5hmC如何调节神经元活动和脑功能，并强调它们在人类神经发育和神经退行性疾病中的意义。最后，我们提出了该领域尚未解决的问题，并展望了关于5hmC和TET酶在神经发育中作用的新研究方向。
