Recently, it has been progressively recognized that gene expression is regulated by histone methylation status, which is dynamically modulated by histone methyltransferases (HMTs) and histone demethylases (HDMs). In the past decade, many HMTs and HDMs were identified and their biological and biochemical functions have been characterized. As with other cells, several HMTs and HDMs are known to be indispensable for appropriate differentiation of adipocytes from mesenchymal stem cells. Phf2 is a recently identified dimethylated histone H3 lysine 9 (H3K9me2) demethylase that has a significant function in hepatocytes and macrophages in vitro; however, the in vivo significance of Phf2 remains unclear. To determine the physiological role of Phf2, we recently generated Phf2 knockout mice. Our analyses of these mice revealed that Phf2 has a positive role in adipogenesis by coactivating CEBPA, one of the master regulators of adipogenesis, through its demethylation activity toward H3K9me2. In this commentary, we discuss several remaining questions that underlie phenotypic abnormalities seen in our investigations of Phf2 knockout mice. These studies are related to novel functions of histone modifiers and may help identify new therapeutic targets for metabolic syndrome.
Keywords: PHF2; adipogenesis; histone demethylation; histone modification; knockout mice.