Control of differentiation in a self-renewing mammalian tissue by the histone demethylase JMJD3
Control of differentiation in a self-renewing mammalian tissue by the histone demethylase JMJD3
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DOI：
10.1101/gad.1673508
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发表时间：
2008-07-15
影响因子：
10.5
通讯作者：
Khavari, Paul A.
中科院分区：
文献类型：
--
作者：
Sen, George L.;Webster, Daniel E.;Khavari, Paul A.
最近发现的 H3K27me3 去甲基酶表明 H3K27me3 可能动态调节基因表达，但这种在哺乳动物组织稳态中的潜在作用仍未得到表征。在表皮中，平衡干细胞自我更新与分化的组织H3K27me3占据了许多分化基因的启动子。在钙诱导分化过程中，H3K27me3 在这些启动子处被擦除，同时 PcG 蛋白占据的丧失和 H3K27me3 去甲基酶 JMJD3 的结合增加。在表皮组织内，JMJD3 缺失会阻碍分化，而活跃的 JMJD3 主要诱导分化。这些结果表明 JMJD3 的表观遗传去抑制控制哺乳动物表皮分化。
The recent discovery of H3K27me3 demethylases suggests that H3K27me3 may dynamically regulate gene expression, but this potential role in mammalian tissue homeostasis remains uncharacterized. In the epidermis, a tissue that balances stem cell self-renewal with differentiation, H3K27me3, occupies the promoters of many differentiation genes. During calcium-induced differentiation, H3K27me3 was erased at these promoters in concert with loss of PcG protein occupancy and increased binding by the H3K27me3 demethylase, JMJD3. Within epidermal tissue, JMJD3 depletion blocked differentiation, while active JMJD3 dominantly induced it. These results indicate that epigenetic derepression by JMJD3 controls mammalian epidermal differentiation.