Features of the PHF8/KIAA1718 histone demethylase

PHD Finger Protein 2 (PHF2) Represses Ribosomal RNA Gene Transcription by Antagonizing PHF Finger Protein 8 (PHF8) and Recruiting Methyltransferase SUV39H1

“…1E). Also in agreement with the previous report (17), deletion of PHD domain or mutation of a single key residue, Met 20 , to alanine within the PHD domain abolished the preferential H3K4me3 binding activity of PHF2 (Fig. 1E).…”

“…PHF2 (also known as JHDM1E and KDM7B), PHF8 (also known as JHDM1F and KDM7C), and KIAA1718 (also known as JHDM1D and KDM7A) are more closely related members of the ␣-ketoglutarate/Fe 2ϩ -dependent dioxygenases characterized by the presence of a Jumonji domain (19,20). Many but not all proteins of this family have been shown to possess histone/non-histone demethylase activity.…”

Stabilization of histone demethylase PHF8 by USP7 promotes breast carcinogenesis

“…In USP7-deficient cells, PHF8 is downregulated, and the downregulation of PHF8 in these cells could be reverted by forced expression of USP7/WT, but not USP7/C223S (Supplemental Figure 3A), while the mRNA expression level of PHF8 was essentially unchanged (Supplemental Figure 3B). Moreover, treatment of MCF-7 cells with HBX 41,108, a cyanoindenopyrazine-derived deubiquitinase inhibitor known to inhibit catalytic activity of USP7 (34), resulted in a dose-dependent ity of PHF8 toward histone modifications (8,9) and in support of our observation that PHF8 is stabilized by USP7, we found that USP7 depletion was associated with increased levels of H3K9me1, H3K9me2, H3K27me2, and H4K20me1, but not H3K4me2 (Figure 2H and Supplemental Figure 2, A and B). This effect faithfully mimicked that of PHF8 depletion ( Figure 2H and Supplemental Figure 2, A and B).…”

“…To this end, endonuclease I-SceI was cotransfected with siRNA targeting 3′-UTR of PHF8 mRNA into DR-GFP U2OS cells stably expressing wild-type PHF8 (PHF8/WT) or demethylase activity-defective PHF8 (PHF8/H247A) (8,9). FACS analysis revealed that PHF8/ WT was able to restore the decreased HR repair efficiency induced by endogenous PHF8 depletion, whereas PHF8/ H247A was not (Supplemental Figure 8A, left panel).…”

“…Among these demethylases, plant homeodomain finger-containing protein 8 (PHF8, also termed KDM7B) is a ubiquitously expressed nuclear protein consisting of an N-terminal plant homeodomain, which recognizes and binds histone H3 lysine 4 tri-methyl (H3K4me3) bearing nucleosomes at transcription start sites (6), and a JmjC domain catalyzing the removal of the methyl moieties from H3K9me1/2, H4K20me1, or H3K27me2 (7)(8)(9)(10). Specifically, PHF8 interacts with PML-RARα and functions as a transcriptional coactivator in response to all-trans retinoic acid treatment (11).…”