Cdx4 和 menin 共同调节造血细胞中 Hoxa9 的表达。
Cdx4 and menin co-regulate Hoxa9 expression in hematopoietic cells.
机构信息
Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
出版信息
PLoS One. 2006 Dec 20;1(1):e47. doi: 10.1371/journal.pone.0000047.
BACKGROUND
Transcription factor Cdx4 and transcriptional coregulator menin are essential for Hoxa9 expression and normal hematopoiesis. However, the precise mechanism underlying Hoxa9 regulation is not clear.
METHODS AND FINDINGS
Here, we show that the expression level of Hoxa9 is correlated with the location of increased trimethylated histone 3 lysine 4 (H3K4M3). The active and repressive histone modifications co-exist along the Hoxa9 regulatory region. We further demonstrate that both Cdx4 and menin bind to the same regulatory region at the Hoxa9 locus in vivo, and co-activate the reporter gene driven by the Hoxa9 cis-elements that contain Cdx4 binding sites. Ablation of menin abrogates Cdx4 access to the chromatin target and significantly reduces both active and repressive histone H3 modifications in the Hoxa9 locus.
CONCLUSION
These results suggest a functional link among Cdx4, menin and histone modifications in Hoxa9 regulation in hematopoietic cells.
背景
转录因子 Cdx4 和转录共激活因子 menin 对于 Hoxa9 的表达和正常造血是必需的。然而，Hoxa9 调控的确切机制尚不清楚。
方法和发现
在这里，我们表明 Hoxa9 的表达水平与 H3K4M3 增加的位置相关。活性和抑制性组蛋白修饰沿着 Hoxa9 调控区共存。我们进一步证明，Cdx4 和 menin 都在体内与 Hoxa9 基因座上的相同调控区结合，并共同激活含有 Cdx4 结合位点的 Hoxa9 顺式元件驱动的报告基因。menin 的缺失消除了 Cdx4 对染色质靶标的接近，并显著降低了 Hoxa9 基因座中活性和抑制性组蛋白 H3 修饰。
结论
这些结果表明在造血细胞中，Cdx4、menin 和组蛋白修饰在 Hoxa9 调控中存在功能联系。
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