| 9586746 | Polycomblike protein PHF1b: a transcriptional sensor for GABA receptor activity. | Saha S, etal., BMC Pharmacol Toxicol. 2013 Jul 23;14:37. doi: 10.1186/2050-6511-14-37. | BACKGROUND: The gamma-aminobutyric acid (GABA) type A receptor (GABA(A)R) contains the recognition sites for a variety of agents used in the treatment of brain disorders, including anxiety and epilepsy. A better understanding of how receptor expression is regulated in individual neurons may provide novel opportunities for therapeutic intervention. Towards this goal we have studied transcription of a GABA(A)R subunit gene (GABRB1) whose activity is autologously regulated by GABA via a 10 base pair initiator-like element (beta(1)-INR). METHODS: By screening a human cDNA brain library with a yeast one-hybrid assay, the Polycomblike (PCL) gene product PHD finger protein transcript b (PHF1b) was identified as a beta(1)-INR associated protein. Promoter/reporter assays in primary rat cortical cells demonstrate that PHF1b is an activator at GABRB1, and chromatin immunoprecipitation assays reveal that presence of PHF1 at endogenous Gabrb1 is regulated by GABA(A)R activation. RESULTS: PCL is a member of the Polycomb group required for correct spatial expression of homeotic genes in Drosophila. We now show that PHF1b recognition of beta(1)-INR is dependent on a plant homeodomain, an adjacent helix-loop-helix, and short glycine rich motif. In neurons, it co-immunoprecipitates with SUZ12, a key component of the Polycomb Repressive Complex 2 (PRC2) that regulates a number of important cellular processes, including gene silencing via histone H3 lysine 27 trimethylation (H3K27me3). CONCLUSIONS: The observation that chronic exposure to GABA reduces PHF1 binding and H3K27 monomethylation, which is associated with transcriptional activation, strongly suggests that PHF1b may be a molecular transducer of GABA(A)R function and thus GABA-mediated neurotransmission in the central nervous system. | 23879974 | 1000-10-01 |
| 11344225 | [PHF10 isoforms are phosphorylated in the PBAF mammalian chromatin remodeling complex]. | Brechalov AV, etal., Mol Biol (Mosk). 2016 Mar-Apr;50(2):320-6. doi: 10.7868/S0026898416010031. | Chromatin remodeling complex PBAF(SWI/SNF) alters the structure of chromatin and controls gene expression. PHF10 is a specific subunit of PBAF complex and is expressed as four isoforms in mammalian cells. We demonstrated that all isoforms are expressed in variou s human cell types of different histological origins. All four isoforms are extensively phosphorylated and their phosphorylation level is depended on the cell type. Phosphorylation of PHF10 isoforms occurs while they are incorporated as a subunit of the PBAF complex, and therefore phosphorylation of PHF10 isoforms may play an essential role in regulation of PBAF complex's function and mechanism of action. | 27239853 | 0001-12-01 |
| 11052595 | MicroRNA-195-5p acts as an anti-oncogene by targeting PHF19 in hepatocellular carcinoma. | Xu H, etal., Oncol Rep. 2015 Jul;34(1):175-82. doi: 10.3892/or.2015.3957. Epub 2015 May 7. | Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. PHD finger protein 19 (PHF19) encodes a member of the polycomb group (PcG) of proteins that functions by maintaining the repressive transcriptional states of many developmental regulat ory genes. In addition, it has been shown that miR-195 plays an important role in the molecular etiology of HCC; however, the effect and possible mechanism of PHF19 on HCC is unclear, and the association between PHF19 and miR-195 has seldom been addressed. In the present study, we investigated the carcinogenic activity and mechanism of PHF19 on HCC in vivo and in vitro. Our results showed that PHF19 is a potential target of hsa-miR-195-5p based on a bioinformatic analysis and results of a luciferase reporter assay. PHF19 was downregulated after transfection with hsa-miR-195-5p mimics. Moreover, we demonstrated that overexpression of PHF19 promoted hepatoma cell migration, invasion and proliferation in vitro. In contrast, overexpression of hsa-miR-195-5p in hepatoma cells reduced PHF19 expression, leading to suppression of hepatoma cell invasion, migration and proliferation in vitro. In addition, PHF19 markedly promoted the growth of xenograft tumors, while hsa-miR-195-5p markedly suppressed the growth of xenograft tumors in nude mice. These results provide evidence that PHF19 promotes HCC and is regulated by the tumor-suppressor, miR-195-5p. | 25955388 | 2015-04-01 |
| 4892275 | Polymorphisms of PHF11 and DPP10 are associated with asthma and related traits in a Chinese population. | Gao J, etal., Respiration. 2010;79(1):17-24. Epub 2009 Aug 11. | BACKGROUND: Initial studies by positional cloning have identified the genes encoding the plant homeodomain zinc finger protein 11 (PHF11) and dipeptidyl-peptidase 10 (DPP10) as asthma susceptibility genes. The variants in the two genes have been associated with asthma in several populations of European or Latin American origin. OBJECTIVE: The aim of this study was to assess the common PHF11 and DPP10 polymorphisms for associations to asthma and asthma-related traits in a Han Chinese population. METHODS: We genotyped six polymorphic markers in PHF11 and five polymorphic markers in DPP10 in a Han Chinese case-control cohort consisting of 408 asthma patients and 288 unrelated disease-free controls recruited from the Northern region of China. We analyzed the association between these markers and asthma as well as a number of intermediate, asthma-related traits. Linkage disequilibrium and haplotype patterns were also evaluated. RESULTS: Significant associations were identified between two makers in PHF11 (rs1046295 and rs16659) and asthma susceptibility (odds ratio, OR = 1.32, 95% con fidence interval, CI = 1.06-1.65, p = 0.0096, for rs1046295, and OR = 1.41, 95% CI = 1.12-1.75, p = 0.0026, for rs16659). A strong association was observed between an SNP in DPP10 (rs10208402) and log(e)-transformed total IgE (p = 0.0003) and the percentage of peripheral blood eosinophils (p = 0.0023). A weak association between rs1430090 in DPP10 and forced expiratory volume in 1 s was also observed (p = 0.048). Haplotype analysis revealed two protective haplotypes in PHF11 against asthma. CONCLUSION: The results provide supporting evidence for genetic variants in PHF11 and DPP10 genes underlying asthma susceptibility and asthma-related quantitative traits in a Han Chinese population. | 19672052 | 1000-02-01 |
