Department of Ophthalmology, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, People's Republic of China.
Department of Biological Sciences, Marshall University, Huntington, WV, USA.
Biochem Biophys Res Commun. 2014 Feb 21;444(4):634-7. doi: 10.1016/j.bbrc.2014.01.143. Epub 2014 Jan 31.
Pituitary homeobox 2 (PITX2), a Paired-like homeodomain transcription factor and a downstream effector of Wnt/β-catenin signaling, plays substantial roles in embryonic development and human disorders. The mechanism of its functions, however, is not fully understood. In this study, we demonstrated that PITX2 associated with histone H3 lysine 4 (H3K4) methyltransferase (HKMT) mixed-lineage leukemia 4 (MLL4/KMT2D), Pax transactivation domain-interacting protein (PTIP), and other H3K4·HKMT core subunits. This association of PITX2 with H3K4·HKMT complex was dependent on PITX2's homeodomain. Consistently, the PITX2 protein complex was shown to possess H3K4·HKMT activity. Furthermore, the chromatin immunoprecipitation result revealed co-occupancy of PITX2 and PTIP on the promoter of the PITX2's transcriptional target. Taken together, our data provide new mechanistic perspectives on PITX2's functions and its related biological processes.
垂体同源盒 2（PITX2）是一种配对样同源结构域转录因子，也是 Wnt/β-连环蛋白信号的下游效应物，在胚胎发育和人类疾病中发挥重要作用。然而，其功能机制尚不完全清楚。在本研究中，我们证明 PITX2 与组蛋白 H3 赖氨酸 4（H3K4）甲基转移酶（HKMT）混合谱系白血病 4（MLL4/KMT2D）、Pax 转录激活域相互作用蛋白（PTIP）和其他 H3K4·HKMT 核心亚基相关。PITX2 与 H3K4·HKMT 复合物的这种关联依赖于 PITX2 的同源结构域。一致地，PITX2 蛋白复合物表现出 H3K4·HKMT 活性。此外，染色质免疫沉淀结果显示 PITX2 和 PTIP 在 PITX2 转录靶基因的启动子上共同占据。总之，我们的数据为 PITX2 的功能及其相关生物学过程提供了新的机制观点。
