The Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
FEBS Lett. 2010 Feb 19;584(4):689-93. doi: 10.1016/j.febslet.2010.01.022. Epub 2010 Jan 17.
Chromodomain, helicase, DNA-binding protein 8 (CHD8) is an ATP-dependent chromatin remodeling enzyme that has been demonstrated to exist within a large protein complex which includes WDR5, Ash2L, and RbBP5, members of the Mixed Lineage Leukemia (MLL) histone modifying complexes. Here we show that CHD8 relocalizes to the promoter of the MLL regulated gene HOXA2 upon gene activation. Depletion of CHD8 enhances HOXA2 expression under activating conditions. Furthermore, depletion of CHD8 results in a loss of the WDR5/Ash2L/RbBP5 subcomplex, and consequently H3K4 trimethylation, at the HOXA2 promoter. These studies suggest that CHD8 alters HOXA2 gene expression and regulates the recruitment of chromatin modifying enzymes.
染色质域解旋酶 DNA 结合蛋白 8（CHD8）是一种 ATP 依赖的染色质重塑酶，已被证明存在于一个包含 WDR5、Ash2L 和 RbBP5 的大型蛋白质复合物中，这些都是混合谱系白血病（MLL）组蛋白修饰复合物的成员。在这里，我们发现 CHD8 在基因激活时重新定位到 MLL 调控基因 HOXA2 的启动子上。在激活条件下，CHD8 的耗竭增强了 HOXA2 的表达。此外，CHD8 的耗竭导致 WDR5/Ash2L/RbBP5 亚复合物以及 HOXA2 启动子处的 H3K4 三甲基化丢失。这些研究表明，CHD8 改变 HOXA2 基因表达并调节染色质修饰酶的募集。
