MLL4 结合 TET3。
MLL4 binds TET3.
机构信息
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
出版信息
Structure. 2024 Jun 6;32(6):706-714.e3. doi: 10.1016/j.str.2024.03.005. Epub 2024 Apr 4.
Human mixed lineage leukemia 4 (MLL4), also known as KMT2D, regulates cell type specific transcriptional programs through enhancer activation. Along with the catalytic methyltransferase domain, MLL4 contains seven less characterized plant homeodomain (PHD) fingers. Here, we report that the sixth PHD finger of MLL4 (MLL4) binds to the hydrophobic motif of ten-eleven translocation 3 (TET3), a dioxygenase that converts methylated cytosine into oxidized derivatives. The solution NMR structure of the TET3-MLL4 complex and binding assays show that, like histone H4 tail, TET3 occupies the hydrophobic site of MLL4, and that this interaction is conserved in the seventh PHD finger of homologous MLL3 (MLL3). Analysis of genomic localization of endogenous MLL4 and ectopically expressed TET3 in mouse embryonic stem cells reveals a high degree overlap on active enhancers and suggests a potential functional relationship of MLL4 and TET3.
人混合谱系白血病 4（MLL4），也称为 KMT2D，通过增强子激活调节细胞类型特异性转录程序。除了催化甲基转移酶结构域外，MLL4 还包含七个特征不明显的植物同源结构域（PHD）指。在这里，我们报告 MLL4（MLL4）的第六个 PHD 指与 ten-eleven translocation 3（TET3）的疏水性基序结合，TET3 是一种双加氧酶，可将甲基化胞嘧啶转化为氧化衍生物。TET3-MLL4 复合物的溶液 NMR 结构和结合实验表明，与组蛋白 H4 尾一样，TET3 占据 MLL4 的疏水性位点，并且这种相互作用在同源 MLL3（MLL3）的第七个 PHD 指中保守。对小鼠胚胎干细胞中内源性 MLL4 和异位表达的 TET3 的基因组定位分析显示，在活性增强子上有高度重叠，表明 MLL4 和 TET3 之间存在潜在的功能关系。
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