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PAQR3 modulates H3K4 trimethylation by spatial modulation of the regulatory subunits of COMPASS-like complexes in mammalian cells

文献类型:期刊论文

作者Liu, Chunchun; Zhang, Yuxue; Hou, Yongfan; Shen, Liqiang; Li, Yinlong; Guo, Weiwei; Xu, Daqian; Liu, Gaigai; Zhao, Zilong; Man, Kaiyang
刊名BIOCHEMICAL JOURNAL
出版日期2015
卷号467期号:3页码:415-424
关键词epigenetics Golgi apparatus hypoxia H3 lysine 4 (H3K4) methylation progestin and adipoQ receptors member 3 (PAQR3) transcriptional regulation
英文摘要Histone modification plays important roles in many biological processes such as development and carcinogenesis. Methylation of histone H3 lysine 4 (H3K4) is commonly associated with transcriptional activation of genes. H3K4 methylation in mammalian cells is carried out by COMPASS (complex of proteins associated with Set1)-like complexes that are composed of catalytic subunits such as MLL1 (mixed-lineage leukaemia 1) and multiple regulatory subunits in which WDR5 (WD40 repeat-containing protein 5), RBBP5 (retinoblastoma-binding protein 5), ASH2 (absent, small or homoeotic discs 2) and DPY30 [constituting the WRAD sub-complex (WDR5-ASH2-RBBP5-DPY30 complex)] are the major ones shared from yeast to metazoans. We report, in the present paper, a new mode of spatial regulation of H3K4 methyltransferase complexes. PAQR3 (progestin and adipoQ receptors member 3), a tumour suppressor specifically localized in the Golgi apparatus, negatively regulates H3K4 trimethylation (H3K4me3) in mammalian cells. Consistently, HOXC8 and HOXA9 gene expression was negatively regulated by PAQR3 expression levels. Hypoxia-induced H3K4me3 was augmented by PAQR3 knockdown and suppressed by PAQR3 overexpression in AGS gastric cancer cells. PAQR3 was able to interact directly or indirectly with the four members of the WRAD sub-complex and tether them to the Golgi apparatus, accompanied by reduction in histone methyltransferase activity in the nucleus. PAQR3 also interfered with the interaction of WDR5 with the C-terminus of MLL1 (C-ter). Collectively, our study indicates that PAQR3 negatively modulates H3K4 methylation via altering the subcellular compartmentalization of the core regulatory subunits of the COMPASS-like complexes in mammalian cells.
类目[WOS]Biochemistry & Molecular Biology
关键词[WOS]HISTONE H3 ; METHYLTRANSFERASE ACTIVITY ; LYSINE-4 METHYLATION ; MOLECULAR REGULATION ; GOLGI-APPARATUS ; GENE-EXPRESSION ; ACTIVE GENES ; RKTG ; PROTEINS ; WDR5
收录类别SCI
语种英语
WOS记录号WOS:000353217200005
版本出版稿
源URL[http://202.127.25.144/handle/331004/53]  
专题中国科学院上海生命科学研究院营养科学研究所_信号转导与营养相关疾病研究组
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GB/T 7714
Liu, Chunchun,Zhang, Yuxue,Hou, Yongfan,et al. PAQR3 modulates H3K4 trimethylation by spatial modulation of the regulatory subunits of COMPASS-like complexes in mammalian cells[J]. BIOCHEMICAL JOURNAL,2015,467(3):415-424.
APA Liu, Chunchun.,Zhang, Yuxue.,Hou, Yongfan.,Shen, Liqiang.,Li, Yinlong.,...&Chen, Yan.(2015).PAQR3 modulates H3K4 trimethylation by spatial modulation of the regulatory subunits of COMPASS-like complexes in mammalian cells.BIOCHEMICAL JOURNAL,467(3),415-424.
MLA Liu, Chunchun,et al."PAQR3 modulates H3K4 trimethylation by spatial modulation of the regulatory subunits of COMPASS-like complexes in mammalian cells".BIOCHEMICAL JOURNAL 467.3(2015):415-424.

入库方式: OAI收割

来源:上海营养与健康研究所

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