Regulation of Transcription Factor Yin Yang 1 by SET7/9-mediated Lysine Methylation

Zhang, Wen-juan; Wu, Xiaonan; Shi, Tao-tao; Xu, Huan-teng; Jia, Yi; Shen, Hai‐feng; Huang, Ming‐Feng; Shu, Xing-yi; Wang, Feifei; Peng, Bing‐ling; Xiao, Rong-quan; Gao, Weiwei; Ding, Jian; Li, Wen

doi:10.1038/srep21718

Cited by 32 publications

(33 citation statements)

References 55 publications

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“…7 C ). Subsequently, we constructed PRMT7 truncations encompassing the N‐terminal (aa 1–378, ΔC) and C‐terminal (aa 379–692, ΔN) regions in which the R531 is located (22), and YY1 truncations encompassing the N‐terminal (aa 1–266, ΔC) region that is responsible for transcriptional activation and the C‐terminal (aa 267–414, ΔN) region that is responsible for transcriptional repression (28) (Fig. 7 D ).…”

Section: Resultsmentioning

confidence: 99%

Automethylation of protein arginine methyltransferase 7 and its impact on breast cancer progression

Geng

Zhang

Liu³

et al. 2017

FASEB j.

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Protein arginine methyltransferases (PRMTs) catalyze protein arginine methylation and are linked to carcinogenesis and metastasis. Some members of PRMTs have been found to undergo automethylation; however, the biologic significance of this self-modification is not entirely clear. In this report, we demonstrate that R531 of PRMT7 is self-methylated, both and Automethylation of PRMT7 plays a key role in inducing the epithelial-mesenchymal transition (EMT) program and in promoting the migratory and invasive behavior of breast cancer cells. We also prove in a nude mouse model that expression of wild-type PRMT7 in MCF7 breast cancer cells promotes metastasis , in contrast to the PRMT7 R531K mutant (a mimic of the unmethylated status). Moreover, our immunohistochemical data unravel a close link between PRMT7 automethylation and the clinical outcome of breast carcinomas. Mechanistically, we determine that loss of PRMT7 automethylation leads to the reduction of its recruitment to the E-cadherin promoter by YY1, which consequently derepresses the E-cadherin expression through decreasing the H4R3me2s level. The findings in this work define a novel post-translational modification of PRMT7 that has a promoting impact on breast cancer metastasis.-Geng, P., Zhang, Y., Liu, X., Zhang, N., Liu, Y., Liu, X., Lin, C., Yan, X., Li, Z., Wang, G., Li, Y., Tan, J., Liu, D.-X., Huang, B., Lu, J. Automethylation of protein arginine methyltransferase 7 and its impact on breast cancer progression.

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Section: Resultsmentioning

confidence: 99%

Automethylation of protein arginine methyltransferase 7 and its impact on breast cancer progression

Geng

Zhang

Liu³

et al. 2017

FASEB j.

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“…In addition, YY1 was found to associate with an array of enzymes, which result in a variety of PTMs on YY1, such as poly(ADP-ribosyl)ation, ubiquitination, acetylation, O-linked glycosylation, S-nitrosation, sumoylation, phosphorylation and methylation. These PTMs can either regulate YY1-binding activity with DNA/proteins or YY1 protein stability, therefore regulating YY1 function in gene transcription, cell cycle and apoptosis control [ 24–37 ]. Recently, we reported that YY1 is targeted by SET7/9, and SET7/9-mediated lysine methylation of YY1 is critical for its DNA-binding activity [ 37 ].…”

Section: Introductionmentioning

confidence: 99%

Methylation of transcription factor YY2 regulates its transcriptional activity and cell proliferation

Shi

et al. 2017

Cell Discov

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Yin Yang 1 (YY1) is a multifunctional DNA-binding transcription factor shown to be critical in a variety of biological processes, and its activity and function have been shown to be regulated by multitude of mechanisms, which include but are not limited to post-translational modifications (PTMs), its associated proteins and cellular localization. YY2, the paralog of YY1 in mouse and human, has been proposed to function redundantly or oppositely in a context-specific manner compared with YY1. Despite its functional importance, how YY2’s DNA-binding activity and function are regulated, particularly by PTMs, remains completely unknown. Here we report the first PTM with functional characterization on YY2, namely lysine 247 monomethylation (K247me1), which was found to be dynamically regulated by SET7/9 and LSD1 both in vitro and in cultured cells. Functional study revealed that SET7/9-mediated YY2 methylation regulated its DNA-binding activity in vitro and in association with chromatin examined by chromatin immunoprecipitation coupled with sequencing (ChIP-seq) in cultured cells. Knockout of YY2, SET7/9 or LSD1 by CRISPR (clustered, regularly interspaced, short palindromic repeats)/Cas9-mediated gene editing followed by RNA sequencing (RNA-seq) revealed that a subset of genes was positively regulated by YY2 and SET7/9, but negatively regulated by LSD1, which were enriched with genes involved in cell proliferation regulation. Importantly, YY2-regulated gene transcription, cell proliferation and tumor growth were dependent, at least partially, on YY2 K247 methylation. Finally, somatic mutations on YY2 found in cancer, which are in close proximity to K247, altered its methylation, DNA-binding activity and gene transcription it controls. Our findings revealed the first PTM with functional implications imposed on YY2 protein, and linked YY2 methylation with its biological functions.

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“…76,77 In addition, SETD7 methylates several nonhistone proteins, including p53, 78 retinoblastoma (RB), 79 NF-jB subunit p65, 80 TAF10, 81 ARTD1, 82 estrogen receptor (ER), 83 HIF-1a, 84 STAT3, 85 DNMT1, 86 SOX2, 87 SUV39H1, 88 PGC-1a, 89 b-catenin, 90 IFITM3, 91 FOXO3, 92 and YY1. 93 Despite the large number of substrates, SETD7's exact in vivo function remains largely undetermined. SETD7 knockout mouse models have no obvious developmental defects and show no apparent deficiencies in DNA damage and p53 responses.…”

Section: Fig 2 Histone Lysine Methyltransferases (Kmt) Andmentioning

confidence: 99%

Host Methyltransferases and Demethylases: Potential New Epigenetic Targets for HIV Cure Strategies and Beyond

Boehm

Ott

2017

AIDS Research and Human Retroviruses

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A successful HIV cure strategy may require reversing HIV latency to purge hidden viral reservoirs or enhancing HIV latency to permanently silence HIV transcription. Epigenetic modifying agents show promise as antilatency therapeutics in vitro and ex vivo, but also affect other steps in the viral life cycle. In this review, we summarize what we know about cellular DNA and protein methyltransferases (PMTs) as well as demethylases involved in HIV infection. We describe the biology and function of DNA methyltransferases, and their controversial role in HIV infection. We further explain the biology of PMTs and their effects on lysine and arginine methylation of histone and nonhistone proteins. We end with a focus on protein demethylases, their unique modes of action and their emerging influence on HIV infection. An outlook on the use of methylation-modifying agents in investigational HIV cure strategies is provided.

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Regulation of Transcription Factor Yin Yang 1 by SET7/9-mediated Lysine Methylation

Cited by 32 publications

References 55 publications

Automethylation of protein arginine methyltransferase 7 and its impact on breast cancer progression

Automethylation of protein arginine methyltransferase 7 and its impact on breast cancer progression

Methylation of transcription factor YY2 regulates its transcriptional activity and cell proliferation

Host Methyltransferases and Demethylases: Potential New Epigenetic Targets for HIV Cure Strategies and Beyond

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