The BRCT-domain containing protein PTIP links PAX2 to a histone H3, lysine 4 methyltransferase complex
The BRCT-domain containing protein PTIP links PAX2 to a histone H3, lysine 4 methyltransferase complex
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DOI：
10.1016/j.devcel.2007.09.004
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发表时间：
2007-10-01
影响因子：
11.8
通讯作者：
Dressler, Gregory R.
中科院分区：
文献类型：
--
作者：
Patel, Sanjeevkumar R.;Kim, Doyeob;Dressler, Gregory R.
组蛋白甲基转移酶的MLL家族通过甲基化赖氨酸4（H3K4）上的组蛋白H3来维持活性染色质结构域。MLL复合物如何以时间和组织特异性方式识别特定的染色质结构域仍不清楚。我们表明DNA结合蛋白PAX 2通过普遍表达的核因子PTIP（pax转录激活结构域相互作用蛋白）促进H3 K4甲基转移酶复合物的组装。PTIP与ALR、MLL3和组蛋白甲基转移酶复合物的其他组分共纯化。PTIP促进ALR复合物的组装和PAX2结合DNA元件处的H3K4甲基化。在没有PTIP的情况下，Pax2与该元件结合，但不组装ALR复合物。胚胎致死ptip无效突变体和条件突变体均显示甲基化H3K4水平降低。因此，PTIP将DNA结合发育调节因子与组蛋白甲基转移酶依赖的表观遗传调节连接起来。
The MLL family of histone methyltransferases maintains active chromatin domains by methylating histone H3 on lysine 4 (H3K4). How MLL complexes recognize specific chromatin domains in a temporal and tissue-specific manner remains unclear. We show that the DNA-binding protein PAX2 promotes assembly of an H3K4 methyltransferase complex through the ubiquitously expressed nuclear factor PTIP (pax transcription activation domain interacting protein). PTIP copurifies with ALR, MLL3, and other components of a histone methyltransferase complex. PTIP promotes assembly of the ALR complex and H3K4 methylation at a PAX2-binding DNA element. Without PTIP, Pax2 binds to this element but does not assemble the ALR complex. Embryonic lethal ptip-null mutants and conditional mutants both show reduced levels of methylated H3K4. Thus, PTIP bridges DNA-binding developmental regulators to histone methyltransferase-dependent epigenetic regulation.