PHF2

Last update 08 May 2025

Basic Info

Synonyms

CENP-35, centromere protein 35, GRC5

+ [7]

Introduction

Lysine demethylase that demethylates both histones and non-histone proteins (PubMed:20129925, PubMed:21167174, PubMed:21532585). Enzymatically inactive by itself, and becomes active following phosphorylation by PKA: forms a complex with ARID5B and mediates demethylation of methylated ARID5B (PubMed:21532585). Demethylation of ARID5B leads to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes (PubMed:21532585). The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. PHF2 is recruited to trimethylated 'Lys-4' of histone H3 (H3K4me3) at rDNA promoters and promotes expression of rDNA (PubMed:21532585). Involved in the activation of toll-like receptor 4 (TLR4)-target inflammatory genes in macrophages by catalyzing the demethylation of trimethylated histone H4 lysine 20 (H4K20me3) at the gene promoters (By similarity).

100 Clinical Results associated with PHF2

100 Translational Medicine associated with PHF2

0 Patents (Medical) associated with PHF2

Literatures (Medical) associated with PHF2

08 Jul 2024·Nucleic Acids Research

PHF2 regulates genome topology and DNA replication in neural stem cells via cohesin

Article

Author: Yoon, Jeehyun ; Chuah, You Heng ; Grinchuk, Oleg V ; Feng, Jia ; Ling, Shuo-Chien ; Teo, Jackie ; Loh, Yuin-Han ; Ng, Shi-Yan ; Sobota, Radoslaw M ; Cipta, Nadia Omega ; Cheok, Chit Fang ; Leung, Jia Yu ; Chong, Zheng-Shan ; Chiu, Hsin Yao ; Lok, Ker-Zhing ; Crasta, Karen Carmelina ; Wang, Loo Chien ; Sanford, Emma May ; Liang, Yajing ; Taneja, Reshma ; Neo, Cheryl Jia Yi ; Tay, Emmy Xue Yun ; Khong, Zi Jian ; Zhao, Tianyun ; Warrier, Tushar ; Tergaonkar, Vinay ; Zheng, Zong-Qing ; Ong, Derrick Sek Tong ; Elfar, Gamal Ahmed Rashed Elsayed ; Lim, Yan Ting ; Zeng, Yingying

AbstractCohesin plays a crucial role in the organization of topologically-associated domains (TADs), which influence gene expression and DNA replication timing. Whether epigenetic regulators may affect TADs via cohesin to mediate DNA replication remains elusive. Here, we discover that the histone demethylase PHF2 associates with RAD21, a core subunit of cohesin, to regulate DNA replication in mouse neural stem cells (NSC). PHF2 loss impairs DNA replication due to the activation of dormant replication origins in NSC. Notably, the PHF2/RAD21 co-bound genomic regions are characterized by CTCF enrichment and epigenomic features that resemble efficient, active replication origins, and can act as boundaries to separate adjacent domains. Accordingly, PHF2 loss weakens TADs and chromatin loops at the co-bound loci due to reduced RAD21 occupancy. The observed topological and DNA replication defects in PHF2 KO NSC support a cohesin-dependent mechanism. Furthermore, we demonstrate that the PHF2/RAD21 complex exerts little effect on gene regulation, and that PHF2’s histone-demethylase activity is dispensable for normal DNA replication and proliferation of NSC. We propose that PHF2 may serve as a topological accessory to cohesin for cohesin localization to TADs and chromatin loops, where cohesin represses dormant replication origins directly or indirectly, to sustain DNA replication in NSC.

01 Apr 2024·Journal of Biochemical and Molecular Toxicology

Novel furan chalcone modulates PHD‐2 induction to impart antineoplastic effect in mammary gland carcinoma

Article

Author: Saeedan, Abdulaziz S ; Ansari, Mohd Nazam ; Kaithwas, Gaurav ; Rastogi, Shubham ; Singh, Sunil Kumar ; Mukerjee, Alok

AbstractNormoxic inactivation of prolyl hydroxylase‐2 (PHD‐2) in tumour microenvironment paves the way for cancer cells to thrive under the influence of HIF‐1α and NF‐κB. Henceforth, the present study is aimed to identify small molecule activators of PHD‐2. A virtual screening was conducted on a library consisting of 265,242 chemical compounds, with the objective of identifying molecules that exhibit structural similarities to the furan chalcone scaffold. Further, PHD‐2 activation potential of screened compound was determined using in vitro 2‐oxoglutarate assay. The cytotoxic activity and apoptotic potential of screened compound was determined using various staining techniques, including 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide, 4′,6‐diamidino‐2‐phenylindole (DAPI), 1,1′,3,3′‐tetraethylbenzimi‐dazolylcarbocyanine iodide (JC‐1), and acridine orange/ethidium bromide (AO/EB), against MCF‐7 cells. 7,12‐Dimethylbenz[a]anthracene (DMBA) model of mammary gland cancer was used to study the in vivo antineoplastic efficacy of screened compound. [(E)‐1‐(4‐fluorophenyl)‐3‐(furan‐2‐yl) prop‐2‐en‐1‐one] (BBAP‐7) was screened and validated as a PHD‐2 activator by an in vitro 2‐oxo‐glutarate assay. The IC50 of BBAP‐7 on MCF‐7 cells is 18.84 µM. AO/EB and DAPI staining showed nuclear fragmentation, blebbing and condensation in MCF‐7 cells following BBAP‐7 treatment. The red‐to‐green intensity ratio of JC‐1 stained MCF‐7 cells decreased after BBAP‐7 treatment, indicating mitochondrial‐mediated apoptosis. DMBA caused mammary gland dysplasia, duct hyperplasia and ductal carcinoma in situ. Carmine staining, histopathology, and scanning electron microscopy demonstrated that BBAP‐7, alone or with tirapazamine, restored mammary gland surface morphology and structural integrity. Additionally, BBAP‐7 therapy significantly reduced oxidative stress and glycolysis. The findings reveal that BBAP‐7 activates PHD‐2, making it a promising anticancer drug.

01 Mar 2024·Cytokine

The H3K9 demethylase plant homeodomain finger protein 2 regulates interleukin 4 production in CD4+ T cells

Article

Author: Tano, Yuzuki ; Watanabe, Mikio ; Fujii, Moe ; Norimatsu, Yoshiaki ; Yasukawa, Masaki ; Yamada, Takeshi ; Arakawa, Yuya ; Imai, Yuuki

CD4⁺ T cells play a key role in the immune response via their differentiation into various helper T cell subsets that produce characteristic cytokines. Epigenetic changes in CD4⁺ T cells are responsible for cytokine production in these subsets, although the exact molecular mechanisms remain unclear. Therefore, we investigated the effects of plant homeodomain finger protein 2 (PHF2), a histone H3K9 demethylase, on cytokine production in CD4⁺ T cells using T cell-specific Phf2-conditional knockout (cKO) mice in this study. we showed that interleukin 4 (Il4) expression was significantly decreased in Phf2-cKO CD4⁺ T cells compared to that in wild-type cells. To further elucidate the role of PHF2 in vivo, we assessed immune responses in a mouse model of ovalbumin (OVA)-induced atopic dermatitis. Phf2-cKO mice exhibited lower serum levels of OVA-specific IgE than those in wild-type mice. These findings suggest that PHF2 plays a role in promoting T helper 2 cell (Th2) function and may contribute to the pathogenesis of Th2-related allergies such as atopic dermatitis. This study demonstrated the impact of PHF2 on cytokine production in CD4⁺ T cells for the first time. Further studies on the PHF2-mediated epigenetic mechanisms may lead to the development of treatments for a variety of immune diseases.

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PHF2

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