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Published in: Digestive Diseases and Sciences 8/2019

01-08-2019 | Epigenetics | Original Article

H3K9me3, H3K36me3, and H4K20me3 Expression Correlates with Patient Outcome in Esophageal Squamous Cell Carcinoma as Epigenetic Markers

Authors: Menghan Zhou, Yiping Li, Shaofeng Lin, Yanping Chen, Yanyan Qian, Zhujiang Zhao, Hong Fan

Published in: Digestive Diseases and Sciences | Issue 8/2019

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Abstract

Background

Histone methylation, as an essential pattern of posttranslational modifications, contributes to multiple cancer-related biological processes. Dysregulation of histone methylation is now considered a biomarker for cancer prognosis.

Aims

This study investigated and evaluated the potential role of four histone lysine trimethylation markers as biomarkers for esophageal squamous cell carcinoma (ESCC) prognosis.

Methods

Tissue arrays were made from 135 paraffin-embedded ESCC samples and examined for histone markers by immunohistochemistry, and 10 pairs of cancer and noncancerous mucosa tissues from ESCC patients were investigated with Western blot. Chi-squared test, Kaplan–Meier analysis with log-rank test, and Cox proportional hazard trend analyses were performed to assess the prognostic values of the markers.

Results

Histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 9 trimethylation (H3K9me3), and histone 4 lysine 20 trimethylation (H4K20me3), but not histone 3 lysine 36 trimethylation (H3K36me3), showed stronger immunostaining signals in tumor tissues than in the corresponding adjacent non-neoplastic mucosa tissues. The expression patterns of H3K36me3, H3K9me3, and H4K20me3 correlated with tumor infiltrating depth, lymph node involvement, and pTNM stage. Low-scoring H3K9me3 and H4K20me3 predicted better prognosis, while H3K36me3 manifested the opposite trend. Poor prognosis occurred in ESCC patients with expression patterns of high levels of H3K9me3, high levels of H4K20me3, and low levels of H3K36me3 expression.

Conclusions

H3K9me3, H4K20me3, and H3K36me3 showed a close relationship with clinical features and were considered independent risk factors for survival of ESCC patients. The combination of H3K9me3, H4K20me3, and H3K36me3 expression, rather than the expression of a single histone marker, is believed to further enhance evaluations of ESCC prognosis and management.
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Literature
1.
go back to reference Bernard WS, Christopher PW. World cancer report. Lyon: International Agency for Research on Cancer; 2014. Bernard WS, Christopher PW. World cancer report. Lyon: International Agency for Research on Cancer; 2014.
3.
4.
go back to reference Katoh H, Qin ZS, Liu R, et al. FOXP3 orchestrates H4K16 acetylation and H3K4 tri-methylation for activation of multiple genes through recruiting MOF and causing displacement of PLU-1. Mol Cell. 2011;44:770–784.CrossRefPubMedPubMedCentral Katoh H, Qin ZS, Liu R, et al. FOXP3 orchestrates H4K16 acetylation and H3K4 tri-methylation for activation of multiple genes through recruiting MOF and causing displacement of PLU-1. Mol Cell. 2011;44:770–784.CrossRefPubMedPubMedCentral
5.
go back to reference Zee BM, Levin RS, Xu B, LeRoy G, Wingreen NS, Garcia BA. In vivo residue-specific histone methylation dynamics. J Biol Chem. 2010;285:3341–3350.CrossRefPubMed Zee BM, Levin RS, Xu B, LeRoy G, Wingreen NS, Garcia BA. In vivo residue-specific histone methylation dynamics. J Biol Chem. 2010;285:3341–3350.CrossRefPubMed
6.
go back to reference Deb M, Kar S, Sengupta D, et al. Chromatin dynamics: H3K4 methylation and H3 variant replacement during development and in cancer. Cell Mol Life Sci. 2014;71:3439–3463.CrossRefPubMed Deb M, Kar S, Sengupta D, et al. Chromatin dynamics: H3K4 methylation and H3 variant replacement during development and in cancer. Cell Mol Life Sci. 2014;71:3439–3463.CrossRefPubMed
7.
go back to reference Bernstein BE, Humphrey EL, Erlich RL, et al. Methylation of histone H3 Lys 4 in coding regions of active genes. Proc Natl Acad Sci USA. 2002;99:8695–8700.CrossRefPubMed Bernstein BE, Humphrey EL, Erlich RL, et al. Methylation of histone H3 Lys 4 in coding regions of active genes. Proc Natl Acad Sci USA. 2002;99:8695–8700.CrossRefPubMed
8.
go back to reference Santos-Rosa H, Schneider R, Bannister AJ, et al. Active genes are tri-methylated at K4 of histone H3. Nature. 2002;419:407–411.CrossRefPubMed Santos-Rosa H, Schneider R, Bannister AJ, et al. Active genes are tri-methylated at K4 of histone H3. Nature. 2002;419:407–411.CrossRefPubMed
9.
go back to reference Chen K, Chen Z, Wu D, et al. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes. Nat Genet. 2015;47:1149–1157.CrossRefPubMedPubMedCentral Chen K, Chen Z, Wu D, et al. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes. Nat Genet. 2015;47:1149–1157.CrossRefPubMedPubMedCentral
10.
go back to reference He C, Xu J, Zhang J, et al. High expression of trimethylated histone H3 lysine 4 is associated with poor prognosis in hepatocellular carcinoma. Hum Pathol. 2012;43:1425–1435.CrossRefPubMed He C, Xu J, Zhang J, et al. High expression of trimethylated histone H3 lysine 4 is associated with poor prognosis in hepatocellular carcinoma. Hum Pathol. 2012;43:1425–1435.CrossRefPubMed
11.
go back to reference Ellinger J, Kahl P, Mertens C, et al. Prognostic relevance of global histone H3 lysine 4 (H3K4) methylation in renal cell carcinoma. Int J Cancer. 2010;127:2360–2366.CrossRefPubMed Ellinger J, Kahl P, Mertens C, et al. Prognostic relevance of global histone H3 lysine 4 (H3K4) methylation in renal cell carcinoma. Int J Cancer. 2010;127:2360–2366.CrossRefPubMed
12.
go back to reference Li GM. Decoding the histone code: role of H3K36me3 in mismatch repair and implications for cancer susceptibility and therapy. Can Res. 2013;73:6379–6383.CrossRef Li GM. Decoding the histone code: role of H3K36me3 in mismatch repair and implications for cancer susceptibility and therapy. Can Res. 2013;73:6379–6383.CrossRef
13.
14.
go back to reference Schotta G, Lachner M, Sarma K, et al. A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. Genes Dev. 2004;18:1251–1262.CrossRefPubMedPubMedCentral Schotta G, Lachner M, Sarma K, et al. A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. Genes Dev. 2004;18:1251–1262.CrossRefPubMedPubMedCentral
15.
go back to reference Shi Y, Whetstine JR. Dynamic regulation of histone lysine methylation by demethylases. Mol Cell. 2007;25:1–14.CrossRefPubMed Shi Y, Whetstine JR. Dynamic regulation of histone lysine methylation by demethylases. Mol Cell. 2007;25:1–14.CrossRefPubMed
16.
go back to reference Rosenfeld JA, Wang Z, Schones DE, Zhao K, DeSalle R, Zhang MQ. Determination of enriched histone modifications in non-genic portions of the human genome. BMC Genom. 2009;10:143.CrossRef Rosenfeld JA, Wang Z, Schones DE, Zhao K, DeSalle R, Zhang MQ. Determination of enriched histone modifications in non-genic portions of the human genome. BMC Genom. 2009;10:143.CrossRef
17.
go back to reference Pauler FM, Sloane MA, Huang R, et al. H3K27me3 forms BLOCs over silent genes and intergenic regions and specifies a histone banding pattern on a mouse autosomal chromosome. Genome Res. 2009;19:221–233.CrossRefPubMedPubMedCentral Pauler FM, Sloane MA, Huang R, et al. H3K27me3 forms BLOCs over silent genes and intergenic regions and specifies a histone banding pattern on a mouse autosomal chromosome. Genome Res. 2009;19:221–233.CrossRefPubMedPubMedCentral
18.
go back to reference Slee RB, Steiner CM, Herbert BS, et al. Cancer-associated alteration of pericentromeric heterochromatin may contribute to chromosome instability. Oncogene. 2012;31:3244–3253.CrossRefPubMed Slee RB, Steiner CM, Herbert BS, et al. Cancer-associated alteration of pericentromeric heterochromatin may contribute to chromosome instability. Oncogene. 2012;31:3244–3253.CrossRefPubMed
19.
go back to reference Peters AH, O’Carroll D, Scherthan H, et al. Loss of the Suv39 h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell. 2001;107:323–337.CrossRef Peters AH, O’Carroll D, Scherthan H, et al. Loss of the Suv39 h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell. 2001;107:323–337.CrossRef
20.
21.
go back to reference Benard A, Goossens-Beumer IJ, van Hoesel AQ, et al. Histone trimethylation at H3K4, H3K9 and H4K20 correlates with patient survival and tumor recurrence in early-stage colon cancer. BMC Cancer. 2014;14:531.CrossRefPubMedPubMedCentral Benard A, Goossens-Beumer IJ, van Hoesel AQ, et al. Histone trimethylation at H3K4, H3K9 and H4K20 correlates with patient survival and tumor recurrence in early-stage colon cancer. BMC Cancer. 2014;14:531.CrossRefPubMedPubMedCentral
22.
go back to reference Jorgensen S, Schotta G, Sorensen CS. Histone H4 lysine 20 methylation: key player in epigenetic regulation of genomic integrity. Nucleic Acids Res. 2013;41:2797–2806.CrossRefPubMedPubMedCentral Jorgensen S, Schotta G, Sorensen CS. Histone H4 lysine 20 methylation: key player in epigenetic regulation of genomic integrity. Nucleic Acids Res. 2013;41:2797–2806.CrossRefPubMedPubMedCentral
23.
go back to reference Ho TH, Kapur P, Joseph RW, et al. Loss of histone H3 lysine 36 trimethylation is associated with an increased risk of renal cell carcinoma-specific death. Mod Pathol. 2016;29:34–42.CrossRefPubMed Ho TH, Kapur P, Joseph RW, et al. Loss of histone H3 lysine 36 trimethylation is associated with an increased risk of renal cell carcinoma-specific death. Mod Pathol. 2016;29:34–42.CrossRefPubMed
24.
go back to reference Munshi A, Shafi G, Aliya N, Jyothy A. Histone modifications dictate specific biological readouts. J Genet Genomics. 2009;36:75–88.CrossRefPubMed Munshi A, Shafi G, Aliya N, Jyothy A. Histone modifications dictate specific biological readouts. J Genet Genomics. 2009;36:75–88.CrossRefPubMed
25.
go back to reference Black JC, Van Rechem C, Whetstine JR. Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol Cell. 2012;48:491–507.CrossRefPubMed Black JC, Van Rechem C, Whetstine JR. Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol Cell. 2012;48:491–507.CrossRefPubMed
26.
go back to reference Lehnertz B, Ueda Y, Derijck AA, et al. Suv39 h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol. 2003;13:1192–1200.CrossRefPubMed Lehnertz B, Ueda Y, Derijck AA, et al. Suv39 h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol. 2003;13:1192–1200.CrossRefPubMed
28.
go back to reference Paschall AV, Yang D, Lu C, et al. H3K9 trimethylation silences Fas expression to confer colon carcinoma immune escape and 5-fluorouracil chemoresistance. J Immunol (Baltimore, Md.: 1950). 2015;195:1868–1882.CrossRef Paschall AV, Yang D, Lu C, et al. H3K9 trimethylation silences Fas expression to confer colon carcinoma immune escape and 5-fluorouracil chemoresistance. J Immunol (Baltimore, Md.: 1950). 2015;195:1868–1882.CrossRef
29.
go back to reference Kylie K, Romero J, Lindamulage IK, Knockleby J, Lee H. Dynamic regulation of histone H3K9 is linked to the switch between replication and transcription at the Dbf4 origin-promoter locus. Cell Cycle (Georgetown, Tex.). 2016;15:2321–2335.CrossRef Kylie K, Romero J, Lindamulage IK, Knockleby J, Lee H. Dynamic regulation of histone H3K9 is linked to the switch between replication and transcription at the Dbf4 origin-promoter locus. Cell Cycle (Georgetown, Tex.). 2016;15:2321–2335.CrossRef
30.
go back to reference Wang DY, An SH, Liu L, et al. Hepatitis B virus X protein influences enrichment profiles of H3K9me3 on promoter regions in human hepatoma cell lines. Oncotarget. 2016;7:84883–84892.PubMedPubMedCentral Wang DY, An SH, Liu L, et al. Hepatitis B virus X protein influences enrichment profiles of H3K9me3 on promoter regions in human hepatoma cell lines. Oncotarget. 2016;7:84883–84892.PubMedPubMedCentral
31.
go back to reference Belyaeva A, Venkatachalapathy S, Nagarajan M, Shivashankar GV, Uhler C. Network analysis identifies chromosome intermingling regions as regulatory hotspots for transcription. Proc Natl Acad Sci USA. 2017;114:13714–13719.CrossRefPubMed Belyaeva A, Venkatachalapathy S, Nagarajan M, Shivashankar GV, Uhler C. Network analysis identifies chromosome intermingling regions as regulatory hotspots for transcription. Proc Natl Acad Sci USA. 2017;114:13714–13719.CrossRefPubMed
32.
go back to reference Brustel J, Kirstein N, Izard F, et al. Histone H4K20 tri-methylation at late-firing origins ensures timely heterochromatin replication. EMBO J. 2017;36:2726–2741.CrossRefPubMedPubMedCentral Brustel J, Kirstein N, Izard F, et al. Histone H4K20 tri-methylation at late-firing origins ensures timely heterochromatin replication. EMBO J. 2017;36:2726–2741.CrossRefPubMedPubMedCentral
33.
go back to reference Nelson DM, Jaber-Hijazi F, Cole JJ, et al. Mapping H4K20me3 onto the chromatin landscape of senescent cells indicates a function in control of cell senescence and tumor suppression through preservation of genetic and epigenetic stability. Genome Biol. 2016;17:158.CrossRefPubMedPubMedCentral Nelson DM, Jaber-Hijazi F, Cole JJ, et al. Mapping H4K20me3 onto the chromatin landscape of senescent cells indicates a function in control of cell senescence and tumor suppression through preservation of genetic and epigenetic stability. Genome Biol. 2016;17:158.CrossRefPubMedPubMedCentral
34.
go back to reference Vieira FQ, Costa-Pinheiro P, Almeida-Rios D, et al. SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets cyclin D2 through H4K20me3. Oncotarget. 2015;6:13644–13657.PubMedPubMedCentral Vieira FQ, Costa-Pinheiro P, Almeida-Rios D, et al. SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets cyclin D2 through H4K20me3. Oncotarget. 2015;6:13644–13657.PubMedPubMedCentral
35.
go back to reference Van Den Broeck A, Brambilla E, Moro-Sibilot D, et al. Loss of histone H4K20 trimethylation occurs in preneoplasia and influences prognosis of non-small cell lung cancer. Clin Cancer Res. 2008;14:7237–7245.CrossRef Van Den Broeck A, Brambilla E, Moro-Sibilot D, et al. Loss of histone H4K20 trimethylation occurs in preneoplasia and influences prognosis of non-small cell lung cancer. Clin Cancer Res. 2008;14:7237–7245.CrossRef
36.
go back to reference Kar S, Patra SK. Overexpression of OCT4 induced by modulation of histone marks plays crucial role in breast cancer progression. Gene. 2018;643:35–45.CrossRefPubMed Kar S, Patra SK. Overexpression of OCT4 induced by modulation of histone marks plays crucial role in breast cancer progression. Gene. 2018;643:35–45.CrossRefPubMed
37.
go back to reference Santos-Barriopedro I, Bosch-Presegue L, Marazuela-Duque A, et al. SIRT6-dependent cysteine monoubiquitination in the PRE-SET domain of Suv39h1 regulates the NF-κB pathway. Nat Commun. 2018;9:101.CrossRefPubMedPubMedCentral Santos-Barriopedro I, Bosch-Presegue L, Marazuela-Duque A, et al. SIRT6-dependent cysteine monoubiquitination in the PRE-SET domain of Suv39h1 regulates the NF-κB pathway. Nat Commun. 2018;9:101.CrossRefPubMedPubMedCentral
38.
go back to reference Keung EZ, Akdemir KC, Al Sannaa GA, et al. Increased H3K9me3 drives dedifferentiated phenotype via KLF6 repression in liposarcoma. J Clin Investig. 2015;125:2965–2978.CrossRefPubMed Keung EZ, Akdemir KC, Al Sannaa GA, et al. Increased H3K9me3 drives dedifferentiated phenotype via KLF6 repression in liposarcoma. J Clin Investig. 2015;125:2965–2978.CrossRefPubMed
39.
go back to reference Yokoyama Y, Matsumoto A, Hieda M, et al. Loss of histone H4K20 trimethylation predicts poor prognosis in breast cancer and is associated with invasive activity. Breast Cancer Res. 2014;16:R66.CrossRefPubMedPubMedCentral Yokoyama Y, Matsumoto A, Hieda M, et al. Loss of histone H4K20 trimethylation predicts poor prognosis in breast cancer and is associated with invasive activity. Breast Cancer Res. 2014;16:R66.CrossRefPubMedPubMedCentral
40.
go back to reference Fraga MF, Ballestar E, Villar-Garea A, et al. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet. 2005;37:391–400.CrossRefPubMed Fraga MF, Ballestar E, Villar-Garea A, et al. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet. 2005;37:391–400.CrossRefPubMed
41.
42.
go back to reference Cao F, Fang Y, Tan HK, et al. Super-enhancers and broad H3K4me3 domains form complex gene regulatory circuits involving chromatin interactions. Sci Rep. 2017;7:2186.CrossRefPubMedPubMedCentral Cao F, Fang Y, Tan HK, et al. Super-enhancers and broad H3K4me3 domains form complex gene regulatory circuits involving chromatin interactions. Sci Rep. 2017;7:2186.CrossRefPubMedPubMedCentral
44.
go back to reference Funata S, Matsusaka K, Yamanaka R, et al. Histone modification alteration coordinated with acquisition of promoter DNA methylation during Epstein-Barr virus infection. Oncotarget. 2017;8:55265–55279.CrossRefPubMedPubMedCentral Funata S, Matsusaka K, Yamanaka R, et al. Histone modification alteration coordinated with acquisition of promoter DNA methylation during Epstein-Barr virus infection. Oncotarget. 2017;8:55265–55279.CrossRefPubMedPubMedCentral
45.
go back to reference Gu P, Chen X, Xie R, et al. lncRNA HOXD-AS1 regulates proliferation and chemo-resistance of castration-resistant prostate cancer via recruiting WDR5. Mol Ther. 2017;25:1959–1973.CrossRefPubMedPubMedCentral Gu P, Chen X, Xie R, et al. lncRNA HOXD-AS1 regulates proliferation and chemo-resistance of castration-resistant prostate cancer via recruiting WDR5. Mol Ther. 2017;25:1959–1973.CrossRefPubMedPubMedCentral
46.
go back to reference Zhang Z, Shi L, Dawany N, Kelsen J, Petri MA, Sullivan KE. H3K4 tri-methylation breadth at transcription start sites impacts the transcriptome of systemic lupus erythematosus. Clin Epigenet. 2016;8:14.CrossRef Zhang Z, Shi L, Dawany N, Kelsen J, Petri MA, Sullivan KE. H3K4 tri-methylation breadth at transcription start sites impacts the transcriptome of systemic lupus erythematosus. Clin Epigenet. 2016;8:14.CrossRef
47.
go back to reference Keogh MC, Kurdistani SK, Morris SA, et al. Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell. 2005;123:593–605.CrossRefPubMed Keogh MC, Kurdistani SK, Morris SA, et al. Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell. 2005;123:593–605.CrossRefPubMed
48.
go back to reference Carrozza MJ, Li B, Florens L, et al. Histone H3 methylation by set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell. 2005;123:581–592.CrossRefPubMed Carrozza MJ, Li B, Florens L, et al. Histone H3 methylation by set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell. 2005;123:581–592.CrossRefPubMed
49.
go back to reference Aymard F, Bugler B, Schmidt CK, et al. Transcriptionally active chromatin recruits homologous recombination at DNA double-strand breaks. Nat Struct Mol Biol. 2014;21:366–374.CrossRefPubMedPubMedCentral Aymard F, Bugler B, Schmidt CK, et al. Transcriptionally active chromatin recruits homologous recombination at DNA double-strand breaks. Nat Struct Mol Biol. 2014;21:366–374.CrossRefPubMedPubMedCentral
50.
go back to reference Chantalat S, Depaux A, Hery P, et al. Histone H3 trimethylation at lysine 36 is associated with constitutive and facultative heterochromatin. Genome Res. 2011;21:1426–1437.CrossRefPubMedPubMedCentral Chantalat S, Depaux A, Hery P, et al. Histone H3 trimethylation at lysine 36 is associated with constitutive and facultative heterochromatin. Genome Res. 2011;21:1426–1437.CrossRefPubMedPubMedCentral
51.
go back to reference Li J, Moazed D, Gygi SP. Association of the histone methyltransferase set2 with RNA polymerase II plays a role in transcription elongation. J Biol Chem. 2002;277:49383–49388.CrossRefPubMed Li J, Moazed D, Gygi SP. Association of the histone methyltransferase set2 with RNA polymerase II plays a role in transcription elongation. J Biol Chem. 2002;277:49383–49388.CrossRefPubMed
52.
go back to reference Li L, Wang Y. Cross-talk between the H3K36me3 and H4K16ac histone epigenetic marks in DNA double-strand break repair. J Biol Chem. 2017;292:11951–11959.CrossRefPubMedPubMedCentral Li L, Wang Y. Cross-talk between the H3K36me3 and H4K16ac histone epigenetic marks in DNA double-strand break repair. J Biol Chem. 2017;292:11951–11959.CrossRefPubMedPubMedCentral
53.
go back to reference Huang Y, Gu L, Li GM. H3K36me3-mediated mismatch repair preferentially protects actively transcribed genes from mutation. J Biol Chem. 2018;293:7811–7823.CrossRefPubMedPubMedCentral Huang Y, Gu L, Li GM. H3K36me3-mediated mismatch repair preferentially protects actively transcribed genes from mutation. J Biol Chem. 2018;293:7811–7823.CrossRefPubMedPubMedCentral
54.
go back to reference Pfister SX, Markkanen E, Jiang Y, et al. Inhibiting WEE1 selectively kills histone H3K36me3-deficient cancers by dNTP starvation. Cancer Cell. 2015;28:557–568.CrossRefPubMedPubMedCentral Pfister SX, Markkanen E, Jiang Y, et al. Inhibiting WEE1 selectively kills histone H3K36me3-deficient cancers by dNTP starvation. Cancer Cell. 2015;28:557–568.CrossRefPubMedPubMedCentral
55.
go back to reference Li F, Mao G, Tong D, et al. The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSalpha. Cell. 2013;153:590–600.CrossRefPubMedPubMedCentral Li F, Mao G, Tong D, et al. The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSalpha. Cell. 2013;153:590–600.CrossRefPubMedPubMedCentral
56.
go back to reference Rogawski DS, Grembecka J, Cierpicki T. H3K36 methyltransferases as cancer drug targets: rationale and perspectives for inhibitor development. Future Med Chem. 2016;8:1589–1607.CrossRefPubMedPubMedCentral Rogawski DS, Grembecka J, Cierpicki T. H3K36 methyltransferases as cancer drug targets: rationale and perspectives for inhibitor development. Future Med Chem. 2016;8:1589–1607.CrossRefPubMedPubMedCentral
Metadata
Title
H3K9me3, H3K36me3, and H4K20me3 Expression Correlates with Patient Outcome in Esophageal Squamous Cell Carcinoma as Epigenetic Markers
Authors
Menghan Zhou
Yiping Li
Shaofeng Lin
Yanping Chen
Yanyan Qian
Zhujiang Zhao
Hong Fan
Publication date
01-08-2019
Publisher
Springer US
Keyword
Epigenetics
Published in
Digestive Diseases and Sciences / Issue 8/2019
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-019-05529-2

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