Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement

Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement
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DOI:
10.1038/ni876
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发表时间:
2003-02-01
期刊:
影响因子:
30.5
通讯作者:
Tarakhovsky, A
Tarakhovsky, A
中科院分区:
医学1区
文献类型:
--
作者:
Su, IH;Basavaraj, A;Tarakhovsky, A

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多梳蛋白家族成员Ezh2是小鼠胚胎发育过程中一种重要的表观遗传调控因子,但其在成年生物体中的作用尚不明确。Ezh2在发育中的小鼠淋巴细胞中高表达,这表明Ezh2参与淋巴细胞生成。通过Cre介导的条件性诱变,我们证明了Ezh2在早期B细胞发育以及免疫球蛋白重链基因(Igh)重排中起关键作用。我们还揭示了Ezh2是早期B细胞祖细胞中组蛋白H3甲基化的关键调控因子。我们的数据表明,依赖于Ezh2的组蛋白H3甲基化是在小鼠早期B细胞发育过程中控制Igh重排的一种新型调控机制。
Polycomb group protein Ezh2 is an essential epigenetic regulator of embryonic development in mice, but its role in the adult organism is unknown. High expression of Ezh2 in developing murine lymphocytes suggests Ezh2 involvement in lymphopoiesis. Using Cre-mediated conditional mutagenesis, we demonstrated a critical role for Ezh2 in early B cell development and rearrangement of the immunoglobulin heavy chain gene (Igh). We also revealed Ezh2 as a key regulator of histone H3 methylation in early B cell progenitors. Our data suggest Ezh2-dependent histone H3 methylation as a novel regulatory mechanism controlling Igh rearrangement during early murine B cell development.