Histone deacetylase inhibitor-based chromatin precipitation for identification of targeted genomic loci
Main Article Content
Keywords
histone deacetylase, chromatin immunoprecipitation, photoreactive probes
Abstract
Histone deacetylase (HDAC) catalyzes the removal of acetyl marks from histones, effectively regulating gene expression. Genome wide chromatin immunoprecipitation (ChIP) studies have shown HDACs are present on numerous active and repressed genes. However, HDAC inhibitors (HDACi) only regulate a small subset of this population in a cell type dependent fashion. To determine genomic locations directly targeted by HDACi, we developed a chromatin precipitation method using a photoreactive HDAC inhibitor probe (photomate). We validate this method by analyzing several canonical HDACi regulated genes, CDKN1A and FOSL1, and compare it to traditional ChIP using HDAC1 antibodies. We show that HDACi target HDACs bound at the promoter regions but not gene bodies, differing from HDAC1 antibody-based ChIP in the case of CDKN1A. This approach is anticipated to be useful for genome wide studies to identify the subset of genes directly regulated by an HDACi in a given cell type.
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References
1. Wang J, Hoshino T, Redner RL, Kajigaya S, Liu JM. ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex. Proceedings of the National Academy of Sciences of the United States of America. 1998 Sep 01;95(18):10860-5. PubMed PMID: 9724795. Pubmed Central PMCID: 27986.
2. Zhang Z, Yamashita H, Toyama T, Sugiura H, Ando Y, Mita K, et al. Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast*. Breast cancer research and treatment. 2005 Nov;94(1):11-6. PubMed PMID: 16172792.
3. Mottamal M, Zheng SL, Huang TL, Wang GD. Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents. Molecules. 2015 Mar;20(3):3898-941. PubMed PMID: WOS:000352471300024. English.
4. Khan DH, Davie JR. HDAC inhibitors prevent the induction of the immediate-early gene FOSL1, but do not alter the nucleosome response. FEBS letters. 2013 May 21;587(10):1510-7. PubMed PMID: 23542037.
5. Hnilicova J, Hozeifi S, Duskova E, Icha J, Tomankova T, Stanek D. Histone deacetylase activity modulates alternative splicing. PloS one. 2011 Feb 02;6(2):e16727. PubMed PMID: 21311748. Pubmed Central PMCID: 3032741.
6. Wang ZB, Zang CZ, Cui KR, Schones DE, Barski A, Peng WQ, et al. Genome-wide Mapping of HATs and HDACs Reveals Distinct Functions in Active and Inactive Genes. Cell. 2009 Sep 4;138(5):1019-31. PubMed PMID: WOS:000269564600025. English.
7. Van Lint C, Emiliani S, Verdin E. The expression of a small fraction of cellular genes is changed in response to histone hyperacetylation. Gene expression. 1996;5(4-5):245-53. PubMed PMID: 8723390. Epub 1996/01/01. eng.
8. Richon VM, Sandhoff TW, Rifkind RA, Marks PA. Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation. Proceedings of the National Academy of Sciences of the United States of America. 2000 Aug 29;97(18):10014-9. PubMed PMID: 10954755. Pubmed Central PMCID: 27656.
9. Chambers AE, Banerjee S, Chaplin T, Dunne J, Debernardi S, Joel SP, et al. Histone acetylation-mediated regulation of genes in leukaemic cells. European journal of cancer. 2003 May;39(8):1165-75. PubMed PMID: 12736119.
10. Mitsiades CS, Mitsiades NS, McMullan CJ, Poulaki V, Shringarpure R, Hideshima T, et al. Transcriptional signature of histone deacetylase inhibition in multiple myeloma: biological and clinical implications. Proceedings of the National Academy of Sciences of the United States of America. 2004 Jan 13;101(2):540-5. PubMed PMID: 14695887. Pubmed Central PMCID: 327183.
11. Peart MJ, Smyth GK, van Laar RK, Bowtell DD, Richon VM, Marks PA, et al. Identification and functional significance of genes regulated by structurally different histone deacetylase inhibitors. Proceedings of the National Academy of Sciences of the United States of America. 2005 Mar 08;102(10):3697-702. PubMed PMID: 15738394. Pubmed Central PMCID: 552783.
12. Sasakawa Y, Naoe Y, Sogo N, Inoue T, Sasakawa T, Matsuo M, et al. Marker genes to predict sensitivity to FK228, a histone deacetylase inhibitor. Biochemical pharmacology. 2005 Feb 15;69(4):603-16. PubMed PMID: 15670579.
13. Ulleras E, Miller SJ, Adam GI, Kanduri C, Wilcock AC, Franklin GC. Inhibition of histone deacetylase activity causes cell type-specific induction of the PDGF-B promoter only in the absence of activation by its enhancer. Experimental cell research. 2001 Nov 01;270(2):188-98. PubMed PMID: 11640883.
14. Li X, Yang H, Huang S, Qiu Y. Histone Deacetylase 1 and p300 Can Directly Associate with Chromatin and Compete for Binding in a Mutually Exclusive Manner. PloS one. 2014;9(4):e94523.
15. Sun Z, Feng D, Fang B, Mullican Shannon E, You S-H, Lim H-W, et al. Deacetylase-Independent Function of HDAC3 in Transcription and Metabolism Requires Nuclear Receptor Corepressor. Molecular Cell. 2013 12/26/;52(6):769-82.
16. Anders L, Guenther MG, Qi J, Fan ZP, Marineau JJ, Rahl PB, et al. Genome-wide localization of small molecules. Nature biotechnology. 2014 Jan;32(1):92-6. PubMed PMID: 24336317. Pubmed Central PMCID: 4189815.
17. Sun JM, Chen HY, Davie JR. Differential distribution of unmodified and phosphorylated histone deacetylase 2 in chromatin. The Journal of biological chemistry. 2007 Nov 09;282(45):33227-36. PubMed PMID: 17827154.
18. Barlev NA, Liu L, Chehab NH, Mansfield K, Harris KG, Halazonetis TD, et al. Acetylation of p53 Activates Transcription through Recruitment of Coactivators/Histone Acetyltransferases. Molecular Cell. 2001 12//;8(6):1243-54.
19. Zupkovitz G, Grausenburger R, Brunmeir R, Senese S, Tischler J, Jurkin J, et al. The cyclin-dependent kinase inhibitor p21 is a crucial target for histone deacetylase 1 as a regulator of cellular proliferation. Molecular and cellular biology. 2010 Mar;30(5):1171-81. PubMed PMID: 20028735. Pubmed Central PMCID: 2820891.
20. Herman D, Jenssen K, Burnett R, Soragni E, Perlman SL, Gottesfeld JM. Histone deacetylase inhibitors reverse gene silencing in Friedreich's ataxia. Nat Chem Biol. 2006 10//print;2(10):551-8.
21. To KKW, Polgar O, Huff LM, Morisaki K, Bates SE. Histone Modifications at the ABCG2 Promoter following Treatment with Histone Deacetylase Inhibitor Mirror Those in Multidrug-Resistant Cells. Molecular Cancer Research. 2008;6(1):151-64.
22. Smith KT, Martin-Brown SA, Florens L, Washburn MP, Workman JL. Deacetylase inhibitors dissociate the histone-targeting ING2 subunit from the Sin3 complex. Chemistry & biology. 2010;17(1):65. PubMed PMID: PMC2819981.
23. Pflum MK, Tong JK, Lane WS, Schreiber SL. Histone deacetylase 1 phosphorylation promotes enzymatic activity and complex formation. The Journal of biological chemistry. 2001 Dec 14;276(50):47733-41. PubMed PMID: 11602581.
24. Liu XF, Bagchi MK. Recruitment of distinct chromatin-modifying complexes by tamoxifen-complexed estrogen receptor at natural target gene promoters in vivo. Journal of Biological Chemistry. 2004 Apr 9;279(15):15050-8. PubMed PMID: WOS:000220594700069. English.
2. Zhang Z, Yamashita H, Toyama T, Sugiura H, Ando Y, Mita K, et al. Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast*. Breast cancer research and treatment. 2005 Nov;94(1):11-6. PubMed PMID: 16172792.
3. Mottamal M, Zheng SL, Huang TL, Wang GD. Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents. Molecules. 2015 Mar;20(3):3898-941. PubMed PMID: WOS:000352471300024. English.
4. Khan DH, Davie JR. HDAC inhibitors prevent the induction of the immediate-early gene FOSL1, but do not alter the nucleosome response. FEBS letters. 2013 May 21;587(10):1510-7. PubMed PMID: 23542037.
5. Hnilicova J, Hozeifi S, Duskova E, Icha J, Tomankova T, Stanek D. Histone deacetylase activity modulates alternative splicing. PloS one. 2011 Feb 02;6(2):e16727. PubMed PMID: 21311748. Pubmed Central PMCID: 3032741.
6. Wang ZB, Zang CZ, Cui KR, Schones DE, Barski A, Peng WQ, et al. Genome-wide Mapping of HATs and HDACs Reveals Distinct Functions in Active and Inactive Genes. Cell. 2009 Sep 4;138(5):1019-31. PubMed PMID: WOS:000269564600025. English.
7. Van Lint C, Emiliani S, Verdin E. The expression of a small fraction of cellular genes is changed in response to histone hyperacetylation. Gene expression. 1996;5(4-5):245-53. PubMed PMID: 8723390. Epub 1996/01/01. eng.
8. Richon VM, Sandhoff TW, Rifkind RA, Marks PA. Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation. Proceedings of the National Academy of Sciences of the United States of America. 2000 Aug 29;97(18):10014-9. PubMed PMID: 10954755. Pubmed Central PMCID: 27656.
9. Chambers AE, Banerjee S, Chaplin T, Dunne J, Debernardi S, Joel SP, et al. Histone acetylation-mediated regulation of genes in leukaemic cells. European journal of cancer. 2003 May;39(8):1165-75. PubMed PMID: 12736119.
10. Mitsiades CS, Mitsiades NS, McMullan CJ, Poulaki V, Shringarpure R, Hideshima T, et al. Transcriptional signature of histone deacetylase inhibition in multiple myeloma: biological and clinical implications. Proceedings of the National Academy of Sciences of the United States of America. 2004 Jan 13;101(2):540-5. PubMed PMID: 14695887. Pubmed Central PMCID: 327183.
11. Peart MJ, Smyth GK, van Laar RK, Bowtell DD, Richon VM, Marks PA, et al. Identification and functional significance of genes regulated by structurally different histone deacetylase inhibitors. Proceedings of the National Academy of Sciences of the United States of America. 2005 Mar 08;102(10):3697-702. PubMed PMID: 15738394. Pubmed Central PMCID: 552783.
12. Sasakawa Y, Naoe Y, Sogo N, Inoue T, Sasakawa T, Matsuo M, et al. Marker genes to predict sensitivity to FK228, a histone deacetylase inhibitor. Biochemical pharmacology. 2005 Feb 15;69(4):603-16. PubMed PMID: 15670579.
13. Ulleras E, Miller SJ, Adam GI, Kanduri C, Wilcock AC, Franklin GC. Inhibition of histone deacetylase activity causes cell type-specific induction of the PDGF-B promoter only in the absence of activation by its enhancer. Experimental cell research. 2001 Nov 01;270(2):188-98. PubMed PMID: 11640883.
14. Li X, Yang H, Huang S, Qiu Y. Histone Deacetylase 1 and p300 Can Directly Associate with Chromatin and Compete for Binding in a Mutually Exclusive Manner. PloS one. 2014;9(4):e94523.
15. Sun Z, Feng D, Fang B, Mullican Shannon E, You S-H, Lim H-W, et al. Deacetylase-Independent Function of HDAC3 in Transcription and Metabolism Requires Nuclear Receptor Corepressor. Molecular Cell. 2013 12/26/;52(6):769-82.
16. Anders L, Guenther MG, Qi J, Fan ZP, Marineau JJ, Rahl PB, et al. Genome-wide localization of small molecules. Nature biotechnology. 2014 Jan;32(1):92-6. PubMed PMID: 24336317. Pubmed Central PMCID: 4189815.
17. Sun JM, Chen HY, Davie JR. Differential distribution of unmodified and phosphorylated histone deacetylase 2 in chromatin. The Journal of biological chemistry. 2007 Nov 09;282(45):33227-36. PubMed PMID: 17827154.
18. Barlev NA, Liu L, Chehab NH, Mansfield K, Harris KG, Halazonetis TD, et al. Acetylation of p53 Activates Transcription through Recruitment of Coactivators/Histone Acetyltransferases. Molecular Cell. 2001 12//;8(6):1243-54.
19. Zupkovitz G, Grausenburger R, Brunmeir R, Senese S, Tischler J, Jurkin J, et al. The cyclin-dependent kinase inhibitor p21 is a crucial target for histone deacetylase 1 as a regulator of cellular proliferation. Molecular and cellular biology. 2010 Mar;30(5):1171-81. PubMed PMID: 20028735. Pubmed Central PMCID: 2820891.
20. Herman D, Jenssen K, Burnett R, Soragni E, Perlman SL, Gottesfeld JM. Histone deacetylase inhibitors reverse gene silencing in Friedreich's ataxia. Nat Chem Biol. 2006 10//print;2(10):551-8.
21. To KKW, Polgar O, Huff LM, Morisaki K, Bates SE. Histone Modifications at the ABCG2 Promoter following Treatment with Histone Deacetylase Inhibitor Mirror Those in Multidrug-Resistant Cells. Molecular Cancer Research. 2008;6(1):151-64.
22. Smith KT, Martin-Brown SA, Florens L, Washburn MP, Workman JL. Deacetylase inhibitors dissociate the histone-targeting ING2 subunit from the Sin3 complex. Chemistry & biology. 2010;17(1):65. PubMed PMID: PMC2819981.
23. Pflum MK, Tong JK, Lane WS, Schreiber SL. Histone deacetylase 1 phosphorylation promotes enzymatic activity and complex formation. The Journal of biological chemistry. 2001 Dec 14;276(50):47733-41. PubMed PMID: 11602581.
24. Liu XF, Bagchi MK. Recruitment of distinct chromatin-modifying complexes by tamoxifen-complexed estrogen receptor at natural target gene promoters in vivo. Journal of Biological Chemistry. 2004 Apr 9;279(15):15050-8. PubMed PMID: WOS:000220594700069. English.
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Published
Mar 30, 2018
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Hanigan TW, Danes JM, Taha TY, Frasor J, Petukhov PA. Histone deacetylase inhibitor-based chromatin precipitation for identification of targeted genomic loci. J Biol Methods [Internet]. 2018 Mar. 30 [cited 2024 Apr. 26];5(1):e88. Available from: https://jbmethods.org/index.php/jbm/article/view/216
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Author Biographies
Thomas W. Hanigan, University of Illinois at Chicago
Department of Medicinal Chemistry and PharmacognosyJeanne M. Danes, University of Illinois at Chicago
Department of Physiology and BiophysicsTaha Y. Taha, University of Illinois at Chicago
Department of Medicinal Chemistry and PharmacognosyPavel A. Petukhov, University of Illinois at Chicago
Department of Medicinal Chemistry and Pharmacognosy
