Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
J Cell Physiol. 2018 Sep;233(9):6841-6852. doi: 10.1002/jcp.26438. Epub 2018 Mar 25.
Plant homeodomain finger 2 (PHF2) is a JmjC family histone demethylase that demethylates H3K9me2, a repressive gene marker. PHF2 was found to play a role in the differentiation of several tissue types such as osteoblast and adipocyte differentiation. We report here that PHF2 plays a role in the epigenetic regulation of megakaryocytic (MK) and erythroid differentiation. We investigated PHF2 expression during MK and erythroid differentiation in K562 and human CD34 progenitor (hCD34 ) cells. Our data demonstrate that PHF2 expression is down-regulated during megakaryopoiesis and erythropoiesis. PHF2 has a negative role in MK and erythroid differentiation of K562 cells; knockdown of PHF2 promotes MK and erythroid differentiation of hCD34 cells. Similarly, we found that p53 expression is also down-regulated during MK and erythroid differentiation, which parallels PHF2 expression. PHF2 binds to the p53 promoter and regulates the expression of p53 by demethylating H3K9me2 in the promoter region of p53. Taken together, our data show that PHF2 is a negative epigenetic regulator of MK and erythroid differentiation, and that one of the pathways through which PHF2 affects MK and erythroid differentiation is via regulation of p53 expression.
植物同源域指 2 型（PHF2）是一个 JmjC 家族的组蛋白去甲基酶，它可以去甲基化 H3K9me2，这是一种抑制基因的标记物。PHF2 被发现参与了几种组织类型的分化，如成骨细胞和脂肪细胞分化。我们在这里报告 PHF2 在巨核细胞（MK）和红细胞分化的表观遗传调控中发挥作用。我们研究了 PHF2 在 K562 和人 CD34 祖细胞（hCD34）细胞中 MK 和红细胞分化过程中的表达情况。我们的数据表明，PHF2 在巨核细胞生成和红细胞生成过程中的表达下调。PHF2 在 K562 细胞的 MK 和红细胞分化中具有负作用；PHF2 的敲低促进了 hCD34 细胞的 MK 和红细胞分化。同样，我们发现 p53 的表达也在 MK 和红细胞分化过程中下调，与 PHF2 的表达相平行。PHF2 结合到 p53 启动子上，并通过去甲基化 p53 启动子区域的 H3K9me2 来调节 p53 的表达。综上所述，我们的数据表明 PHF2 是 MK 和红细胞分化的负表观遗传调节因子，PHF2 影响 MK 和红细胞分化的途径之一是通过调节 p53 的表达。
