Tet1 对于维持多能性是可有可无的，其缺失与胚胎和出生后发育是兼容的。
Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development.
机构信息
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
出版信息
Cell Stem Cell. 2011 Aug 5;9(2):166-75. doi: 10.1016/j.stem.2011.07.010.
Abstract
The Tet family of enzymes (Tet1/2/3) converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Mouse embryonic stem cells (mESCs) highly express Tet1 and have an elevated level of 5hmC. Tet1 has been implicated in ESC maintenance and lineage specification in vitro but its precise function in development is not well defined. To establish the role of Tet1 in pluripotency and development, we have generated Tet1 mutant mESCs and mice. Tet1(-/-) ESCs have reduced levels of 5hmC and subtle changes in global gene expression, and are pluripotent and support development of live-born mice in tetraploid complementation assay, but display skewed differentiation toward trophectoderm in vitro. Tet1 mutant mice are viable, fertile, and grossly normal, though some mutant mice have a slightly smaller body size at birth. Our data suggest that Tet1 loss leading to a partial reduction in 5hmC levels does not affect pluripotency in ESCs and is compatible with embryonic and postnatal development.
摘要
Tet 酶家族（Tet1/2/3）将 5-甲基胞嘧啶（5mC）转化为 5-羟甲基胞嘧啶（5hmC）。小鼠胚胎干细胞（mESCs）高度表达 Tet1，并且 5hmC 水平升高。Tet1 已被牵涉到 ESC 的维持和体外谱系特化，但它在发育中的精确功能尚未明确定义。为了确定 Tet1 在多能性和发育中的作用，我们生成了 Tet1 突变的 mESCs 和小鼠。Tet1(-/-) ESC 的 5hmC 水平降低，并且全局基因表达发生细微变化，具有多能性，并在四倍体互补测定中支持活产小鼠的发育，但在体外向滋养外胚层分化的偏向性增加。Tet1 突变小鼠是存活的、有生育能力的和大体正常的，尽管一些突变小鼠在出生时的体型略小。我们的数据表明，导致 5hmC 水平部分降低的 Tet1 缺失不会影响 ESC 的多能性，并且与胚胎和出生后的发育兼容。
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本文引用的文献
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Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain.TET1 介导的 5-甲基胞嘧啶羟化促进成年大脑中的活性 DNA 去甲基化。
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TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity.TET1 和羟甲基胞嘧啶在转录和 DNA 甲基化保真度中的作用。
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Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation.小鼠胚胎干细胞及其分化过程中 5-羟甲基胞嘧啶的动态调控
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