Department of Biology of the Cell Nucleus, Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic, v.v.i., 142 20 Prague, Czech Republic.
Department of Biology of the Cell Nucleus, Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic, v.v.i., 142 20 Prague, Czech Republic; Department of Epigenetics of the Cell Nucleus, Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic, v.v.i., division BIOCEV, 25250 Vestec, Czech Republic; Microscopy Center the Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic, v.v.i., 142 20 Prague, Czech Republic.
Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Mar;1863(3):266-275. doi: 10.1016/j.bbalip.2017.12.008. Epub 2017 Dec 12.
Phosphoinositides are present in the plasma membrane, cytoplasm and inside the cell nucleus. Here we identify phosphatidylinositol-4,5-bisphosphate (PIP2) as a regulator of rRNA genes transcription at the epigenetic level. We show that PIP2 directly interacts with histone lysine demethylase PHF8 (PHD finger protein 8) and represses demethylation of H3K9me2 through this interaction. We identify the C-terminal K/R-rich motif as PIP2-binding site within PHF8, and address the function of this PIP2-PHF8 complex. PIP2-binding mutant of PHF8 has increased the activity of rDNA promoter (20%) and expression of pre-rRNA genes (47S-100%; 45S-66%). Furthermore, trypsin digestion reveals a potential conformational change of PHF8 upon PIP2 binding. These observations identify the function of nuclear PIP2, and suggest that PIP2 contributes to the fine-tuning of rDNA transcription.
磷脂酰肌醇 4,5-二磷酸（PIP2）存在于质膜、细胞质和细胞核内部。在这里，我们发现 PIP2 可在表观遗传水平上调节 rRNA 基因的转录。我们表明，PIP2 可直接与组蛋白赖氨酸去甲基化酶 PHF8（富含 PHD 指的蛋白 8）相互作用，并通过这种相互作用抑制 H3K9me2 的去甲基化。我们确定了 PHF8 内 PIP2 结合的 C 末端 K/R 富含基序，并解决了这个 PIP2-PHF8 复合物的功能问题。PHF8 的 PIP2 结合突变体增加了 rDNA 启动子（20%）和前 rRNA 基因（47S-100%；45S-66%）的活性。此外，胰蛋白酶消化表明 PIP2 结合后 PHF8 可能发生了构象变化。这些观察结果确定了核 PIP2 的功能，并表明 PIP2 有助于 rDNA 转录的精细调节。
