Methylation of H2AR29 is a novel repressive PRMT6 target

Waldmann, Tanja; Izzo, Annalisa; Kamieniarz, Kinga; Richter, Florian; Vogler, Christine; Sarg, Bettina; Lindner, Herbert; Young, Nicolas L.; Mittler, Gerhard; Garcia, Benjamin A.; Schneider, Robert

doi:10.1186/1756-8935-4-11

Cited by 82 publications

(79 citation statements)

References 28 publications

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“…It is the second smallest member in PRMTs family, containing 375 amino acids. PRMT6 is exclusively located in the nucleus 9 , 10 . Its well-conserved sequence includes the YYECY motif 4 .…”

Section: The Protein Arginine Methyltransferase Familymentioning

confidence: 99%

Protein arginine methylation of non-histone proteins and its role in diseases

et al. 2013

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Protein arginine methyltransferases (PRMTs) are a family of enzymes that can methylate arginine residues on histones and other proteins. PRMTs play a crucial role in influencing various cellular functions, including cellular development and tumorigenesis. Arginine methylation by PRMTs is found on both nuclear and cytoplasmic proteins. Recently, there is increasing evidence regarding post-translational modifications of non-histone proteins by PRMTs, illustrating the previously unknown importance of PRMTs in the regulation of various cellular functions by post-translational modifications. In this review, we present the recent developments in the regulation of non-histone proteins by PRMTs.

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“…It is the second smallest member in PRMTs family, containing 375 amino acids. PRMT6 is exclusively located in the nucleus 9 , 10 . Its well-conserved sequence includes the YYECY motif 4 .…”

Section: The Protein Arginine Methyltransferase Familymentioning

confidence: 99%

Protein arginine methylation of non-histone proteins and its role in diseases

et al. 2013

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“…The H3R2me2a mark is thought to be repressive in nature because of its ability to counteract the activator function of the H3K4me3 mark by inhibiting effector protein recruitment. PRMT6 also deposits the H2AR29me2a mark, which is enriched at the promoters of genes that are transcriptionally repressed by PRMT6 (10). With regard to its activator functions, PRMT6 was identified as a transcriptional coactivator of the estrogen receptor (11), and in this context, its ability to methylate H3R42 may be important.…”

Section: Introductionmentioning

confidence: 99%

A gain-of-function mouse model identifies PRMT6 as a NF-κB coactivator

et al. 2014

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Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that modifies histone tails. To help elucidate the biological function of PRMT6 in vivo, we generated transgenic mice that ubiquitously express PRMT6 fused to the hormone-binding portion of the estrogen receptor (ER*). The ER*-PRMT6 fusion is unstable and cytoplasmic, but upon systemic treatment with tamoxifen, it becomes stabilized and translocates into the nucleus. As a result, a dramatic increase in the H3R2me2a histone mark is observed. We found that one consequence of induced ER*-PRMT6 activation is increased IL-6 levels. IL-6 expression is regulated by the nuclear factor-kappa B (NF-κB) transcription factor, and PRMT6 functions as a coactivator of this pathway. We show that PRMT6 directly interacts with RelA, and that its overexpression enhances the transcriptional activity of an ectopic NF-κB reporter and endogenously regulates NF-κB target genes. PRMT6 is recruited, by RelA, to selective NF-κB target promoters upon TNF-α stimulation. Moreover, ER*-PRMT6 activation causes RelA accumulation in the nucleus. In summary, we observe that PRMT6 is recruited to chromatin at selective NF-κB target promoters, where it likely impacts the histone code and/or methylates other chromatin-associated proteins to facilitate transcription.

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“…HsPRMT6 methylates a few substrates, including HMG1A [8]–[10], DNA polymerase beta [5], tumor repressor p16 [11], histones [12]–[14], and several HIV proteins [15]–[16].…”

Section: Introductionmentioning

confidence: 99%

Crystal Structure of Arginine Methyltransferase 6 from Trypanosoma brucei

et al. 2014

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Arginine methylation plays vital roles in the cellular functions of the protozoan Trypanosoma brucei. The T. brucei arginine methyltransferase 6 (TbPRMT6) is a type I arginine methyltransferase homologous to human PRMT6. In this study, we report the crystal structures of apo-TbPRMT6 and its complex with the reaction product S-adenosyl-homocysteine (SAH). The structure of apo-TbPRMT6 displays several features that are different from those of type I PRMTs that were structurally characterized previously, including four stretches of insertion, the absence of strand β15, and a distinct dimerization arm. The comparison of the apo-TbPRMT6 and SAH-TbPRMT6 structures revealed the fine rearrangements in the active site upon SAH binding. The isothermal titration calorimetry results demonstrated that SAH binding greatly increases the affinity of TbPRMT6 to a substrate peptide derived from bovine histone H4. The western blotting and mass spectrometry results revealed that TbPRMT6 methylates bovine histone H4 tail at arginine 3 but cannot methylate several T. brucei histone tails. In summary, our results highlight the structural differences between TbPRMT6 and other type I PRMTs and reveal that the active site rearrangement upon SAH binding is important for the substrate binding of TbPRMT6.

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Methylation of H2AR29 is a novel repressive PRMT6 target

Cited by 82 publications

References 28 publications

Protein arginine methylation of non-histone proteins and its role in diseases

Protein arginine methylation of non-histone proteins and its role in diseases

A gain-of-function mouse model identifies PRMT6 as a NF-κB coactivator

Crystal Structure of Arginine Methyltransferase 6 from Trypanosoma brucei

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