Enrichment of Cxcl12 promoter with TET2: a possible link between promoter demethylation and enhanced gene expression in the absence of PARP-1

Anja Z. Tolić, Jovana J. Rajić, Marija B. Đorđević, Miloš M. Đorđević, Svetlana S. Dinić, Nevena M. Grdović, Jelena D. Arambašić Jovanović, Mirjana V. Mihailović, Goran Đ. Poznanović, Tomasz P. Jurkowski, Melita S. Vidaković, Aleksandra S. Uskoković

Abstract


Abstract: Previously, we described the link between C-X-C motif chemokine 12 (Cxcl12) gene induction and DNA hypomethylation in the absence of poly(ADP-ribose) polymerase 1 (PARP-1). We have now firmly established that demethylation is the primary cause of gene induction on the basis of Cxcl12 gene upregulation upon treatment with the demethylating agent 5-azacytidine (5-aza). Since the demethylation state of Cxcl12 is favored by PARP-1 absence, we investigated the presence of ten-eleven translocation (TET) proteins on the Cxcl12 promoter in order to corroborate the relationship between the demethylation process and increased gene expression that occurs in the absence of PARP-1. Analysis was performed on the promoter region within CpG islands of Cxcl12 from control mouse embryonic fibroblasts (NIH3T3) and Parp-1 knock-out mouse embryonic fibroblasts (PARP1-/-). The lack of PARP-1 increased the abundance of TET2 on the Cxcl12 promoter, suggesting that TET-mediated demethylation provoked by the absence of PARP-1 could account for the observed increased expression of this chemokine. Deciphering the regulation of DNA (de)methylation factors that control Cxcl12 expression may provide an additional therapeutic approach in pharmacological interventions where gene switching on or off based on targeted stimulation or inhibition is necessary.

https://doi.org/10.2298/ABS190404027T

Received: April 4, 2019; Accepted: April 18, 2019; Published online: April 18, 2019

How to cite this article: Tolić AZ, Rajić JJ, Đorđević MB, Đorđević MM, Dinić SS, Grdović NM, Arambašić-Jovanović JD, Mihailović MV, Poznanović GĐ, Jurkowski TP, Vidaković MS, Uskoković AS.  Enrichment of Cxcl12 promoter with TET2: A possible link between promoter demethylation and enhanced gene expression in the absence of PARP-1. Arch Biol Sci. 2019;71(3):455-62.


Keywords


DNA demethylation; 5-aza; TET2; PARP-1; CXCL12

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References


Goll MG, Bestor TH. Eukaryotic cytosine methyltransferases. Annu Rev Biochem. 2005;74(1):481-514.

Bernstein BE, Meissner A, Lander ES. The mammalian epigenome. Cell. 2007;128(4):669-81.

Williams K, Christensen J, Helin K. DNA methylation: TET proteins-guardians of CpG islands? EMBO Rep. 2012;13(1):28-35.

Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324(5929):930-5.

Ito S, Shen L, Dai Q, Wu SC, Collins LB, Carolina N, Hill C, Swenberg J a, He C, Zhang Y. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333(6047):1300-3.

He Y, Li B-Z, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L, Sun Y, Li X, Dai Q, Song C-X, Zhang K, He C, Xu G-L. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science. 2011;333(6047):1303-7.

Tan L, Shi YG. Tet family proteins and 5-hydroxymethylcytosine in development and disease. Development. 2012;139(11):1895-902.

Kong L, Tan L, Lv R, Shi Z, Xiong L, Wu F, Rabidou K, Smith M, He C, Zhang L, Qian Y, Ma D, Lan F, Shi Y, Shi YG. A primary role of TET proteins in establishment and maintenance of De Novo bivalency at CpG islands. Nucleic Acids Res. 2016;44(18):8682-92.

Caiafa P, Guastafierro T, Zampieri M. Epigenetics: poly(ADP-ribosyl)ation of PARP-1 regulates genomic methylation patterns. FASEB J. 2009;23(3):672-8.

Krishnakumar R, Kraus WL. The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets. Mol Cell. 2010;39(1):8-24.

Ciccarone F, Zampieri M, Caiafa P. PARP1 orchestrates epigenetic events setting up chromatin domains. Semin Cell Dev Biol. 2017;63:123-34.

Tolić A, Grdović N, Dinić S, Rajić J, Đorđević M, Sinadinović M, Arambašić Jovanović J, Mihailović M, Poznanović G, Uskoković A, Vidaković M. Absence of PARP-1 affects Cxcl12 expression by increasing DNA demethylation. J Cell Mol Med. 2019;00:1-9.

Janssens R, Struyf S, Proost P. The unique structural and functional features of CXCL12. Cell Mol Immunol. 2018;15(4):299-311.

Ratajczak MZ, Zuba-Surma E, Kucia M, Reca R, Wojakowski W, Ratajczak J. The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis. Leukemia. 2006;20(11):1915-24.

Liu Z, Habener JF. Stromal cell-derived factor-1 promotes survival of pancreatic beta cells by the stabilisation of beta-catenin and activation of transcription factor 7-like 2 (TCF7L2). Diabetologia. 2009;52(8):1589-98.

Ramos EAS, Camargo AA, Braun K, Slowik R, Cavalli IJ, Ribeiro EMSF, Pedrosa F de O, de Souza EM, Costa FF, Klassen G. Simultaneous CXCL12 and ESR1 CpG island hypermethylation correlates with poor prognosis in sporadic breast cancer. BMC Cancer. 2010;10(1):23.

Li B, Wang Z, Wu H, Xue M, Lin P, Wang S, Lin N, Huang X, Pan W, Liu M, Yan X, Qu H, Sun L, Li H, Wu Y, Teng W, Wang Z, Zhou X, Chen H, Poznansky MC, Ye Z. Epigenetic regulation of CXCL12 plays a critical role in mediating tumor progression and the immune response in osteosarcoma. Cancer Res. 2018;78(14):3938-53.

de Murcia JM, Niedergang C, Trucco C, Ricoul M, Dutrillaux B, Mark M, Oliver FJ, Masson M, Dierich A, LeMeur M, Walztinger C, Chambon P, de Murcia G. Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. Proc Natl Acad Sci U S A. 1997;94(14):7303-7.

Akirav EM, Lebastchi J, Galvan EM, Henegariu O, Akirav M, Ablamunits V, Lizardi PM, Herold KC. Detection of cell death in diabetes using differentially methylated circulating DNA. Proc Natl Acad Sci. 2011;108(47):19018-23.

Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002;3(6):415-28.

Wendt MK, Cooper AN, Dwinell MB. Epigenetic silencing of CXCL12 increases the metastatic potential of mammary carcinoma cells. Oncogene. 2008;27(10):1461-71.

Zhou W, Jiang Z, Liu N, Xu F, Wen P, Liu Y, Zhong W, Song X, Chang X, Zhang X, Wei G, Yu J. Down-regulation of CXCL12 mRNA expression by promoter hypermethylation and its association with metastatic progression in human breast carcinomas. J Cancer Res Clin Oncol. 2009;135(1):91-102.

Vidaković M, Grdović N, Dinić S, Mihailović M, Uskoković A, Arambašić Jovanović J. The Importance of the CXCL12/CXCR4 Axis in Therapeutic Approaches to Diabetes Mellitus Attenuation. Front Immunol. 2015;6:403.

Christman JK, Mendelsohn N, Herzog D, Schneiderman N. Effect of 5-azacytidine on differentiation and DNA methylation in human promyelocytic leukemia cells (HL-60). Cancer Res. 1983;43(2):763-9.

Christman JK. 5-Azacytidine and 5-aza-2′-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy. Oncogene. 2002;21(35):5483-95.

Verma N, Pan H, Doré LC, Shukla A, Li Q V, Pelham-Webb B, Teijeiro V, González F, Krivtsov A, Chang C-J, Papapetrou EP, He C, Elemento O, Huangfu D. TET proteins safeguard bivalent promoters from de novo methylation in human embryonic stem cells. Nat Genet. 2018;50(1):83-95.

Mori T, Kim J, Yamano T, Takeuchi H, Huang S, Umetani N, Koyanagi K, Hoon DSB. Epigenetic Up-regulation of C-C Chemokine Receptor 7 and C-X-C Chemokine Receptor 4 Expression in Melanoma Cells. Cancer Res. 2005;65(5):1800-7.

Wendt MK, Johanesen PA, Kang-Decker N, Binion DG, Shah V, Dwinell MB. Silencing of epithelial CXCL12 expression by DNA hypermethylation promotes colonic carcinoma metastasis. Oncogene. 2006;25(36):4986-97.

Kubarek Ł, Jagodzinski PP. Epigenetic up-regulation of CXCR4 and CXCL12 expression by 17 β-estradiol and tamoxifen is associated with formation of DNA methyltransferase 3B4 splice variant in Ishikawa endometrial adenocarcinoma cells. FEBS Lett. 2007;581(7):1441-8.

Xu Y, Xu C, Kato A, Tempel W, Abreu JG, Bian C, Hu Y, Hu D, Zhao B, Cerovina T, Diao J, Wu F, He HH, Cui Q, Clark E, Ma C, Barbara A, Veenstra GJC, Xu G, Kaiser UB, Liu XS, Sugrue SP, He X, Min J, Kato Y, Shi YG. Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development. Cell. 2012;151(6):1200-13.

Ko M, An J, Bandukwala HS, Chavez L, Aijö T, Pastor WA, Segal MF, Li H, Koh KP, Lähdesmäki H, Hogan PG, Aravind L, Rao A. Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX. Nature. 2013;497(7447):122-6.

Nakagawa T, Lv L, Nakagawa M, Yu Y, Yu C, D’Alessio AC, Nakayama K, Fan H-Y, Chen X, Xiong Y. CRL4(VprBP) E3 ligase promotes monoubiquitylation and chromatin binding of TET dioxygenases. Mol Cell. 2015;57(2):247-60.

Zhang H, Zhang X, Clark E, Mulcahey M, Huang S, Shi YG. TET1 is a DNA-binding protein that modulates DNA methylation and gene transcription via hydroxylation of 5-methylcytosine. Cell Res. 2010;20(12):1390-3.

Xu Y, Wu F, Tan L, Kong L, Xiong L, Deng J, Barbera AJ, Zheng L, Zhang H, Huang S, Min J, Nicholson T, Chen T, Xu G, Shi Y, Zhang K, Shi YG. Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells. Mol Cell. 2011;42(4):451-64.

Rasmussen KD, Helin K. Role of TET enzymes in DNA methylation , development , and cancer. Genes Dev. 2016;30(7):733-50.

Chen L-L, Lin H-P, Zhou W-J, He C-X, Zhang Z-Y, Cheng Z-L, Song J-B, Liu P, Chen X-Y, Xia Y-K, Chen X-F, Sun R-Q, Zhang J-Y, Sun Y-P, Song L, Liu B-J, Du R-K, Ding C, Lan F, Huang S-L, Zhou F, Liu S, Xiong Y, Ye D, Guan K-L. SNIP1 recruits TET2 to regulate c-MYC target genes and cellular DNA damage response. Cell Rep. 2018;25(6):1485-1500.e4.

Hu L, Li Z, Cheng J, Rao Q, Gong W, Liu M, Shi YG, Zhu J, Wang P, Xu Y. Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC oxidation. Cell. 2013;155(7):1545-55.

Müller U, Bauer C, Siegl M, Rottach A, Leonhardt H. TET-mediated oxidation of methylcytosine causes TDG or NEIL glycosylase dependent gene reactivation. Nucleic Acids Res. 2014;42(13):8592-604.

Fujiki K, Shinoda A, Kano F, Sato R, Shirahige K, Murata M. PPARγ-induced PARylation promotes local DNA demethylation by production of 5-hydroxymethylcytosine. Nat Commun. 2013;4:2262.

Nalabothula N, Al-jumaily T, Eteleeb AM, Flight RM, Xiaorong S, Moseley H, Rouchka EC, Fondufe-Mittendorf YN. Genome-wide profiling of PARP1 reveals an interplay with gene regulatory regions and DNA methylation. PLoS One. 2015;10(8):e0135410.


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