超级增强子在肿瘤研究中的进展

doi:10.16288/j.yczz.18-152

遗传 ›› 2019, Vol. 41 ›› Issue (1): 41-51.doi: 10.16288/j.yczz.18-152

超级增强子在肿瘤研究中的进展

吴志强^1,²,米泽云³

^1. 天津医科大学肿瘤医院,放射治疗科,天津 300060
^2. 国家肿瘤临床医学研究中心,天津市“肿瘤防治”重点实验室,天津市恶性肿瘤临床医学研究中心,天津 300060;
^3. 天津医科大学基础医学院,生物化学与分子生物学系,天津 300070

收稿日期:2018-07-13 修回日期:2018-09-21 出版日期:2019-01-20 发布日期:2018-11-05
作者简介:吴志强,博士,讲师,研究方向：放射生物学,肿瘤分子生物学。E-mail: zwu08@tmu.edu.cn
基金资助:
国家自然科学基金项目(编号：81502660,31700144)和天津市自然科学基金项目(编号：16JCQNJC10000, 17JCQNJC10600)资助

Research progress of super enhancer in cancer

Wu Zhiqiang^1,²,Mi Zeyun³

^1. Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China;
^2. Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China;
^3. Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China

Received:2018-07-13 Revised:2018-09-21 Online:2019-01-20 Published:2018-11-05
Supported by:
[Supported by the National Natural Science Foundation of China (Nos. 81502660,31700144) and Tianjin Municipal Science and Technology Commission (Nos. 16JCQNJC10000, 17JCQNJC10600)]

摘要/Abstract

摘要：

超级增强子是由多个相邻近的普通增强子组成的、驱动调控细胞身份基因表达的一个大簇,该区域富集高密度的转录因子、辅因子及增强子相关表观修饰。超级增强子所驱动的异常转录基因对维持肿瘤细胞特性至关重要。肿瘤细胞通过组装自身超级增强子,显著促进多种癌基因表达,从而增强肿瘤细胞的增殖、侵袭和转移的能力;抑制超级增强子的活性,则显著抑制肿瘤细胞的生长和存活。本文对目前报道的肿瘤细胞中超级增强子的结构特征和功能调控,以及靶向超级增强子药物研发现状进行了总结,旨在为研发新的针对超级增强子为靶点的抗肿瘤药物提供理论基础和借鉴。

关键词: 增强子, 超级增强子, 转录, 癌症

Abstract:

Super enhancers (SEs) are composed of clusters of enhancers in close genomic proximity. They constitute a large family of regulatory elements that specify gene expression patterns and cell identity. SE regions consist of unusually strong enrichment of binding sites for transcriptional factors, cofactors, and enhancers associated with epigenetic modifications. SEs play important roles in regulating the aberrant gene expression in tumor cells. Via SEs, cancer cells activate the expression of various oncogenes, and promote cell proliferation, invasion and migration properties. Hence suppression of SEs activities could inhibit the growth and survival of cancer cells. In this review, we summarize the fundamental principles, functions and regulation of super enhancers and therapeutic potential in targeting SEs in cancer cells, thereby introducing and providing new conceptions for development of antineoplastic drugs.

Key words: enhancer, super enhancer, transcription, cancer

吴志强, 米泽云. 超级增强子在肿瘤研究中的进展[J]. 遗传, 2019, 41(1): 41-51.

Wu Zhiqiang, Mi Zeyun. Research progress of super enhancer in cancer[J]. Hereditas(Beijing), 2019, 41(1): 41-51.

参考文献

[1]	Banerji J, Rusconi S, Schaffner W . Expression of a beta- globin gene is enhanced by remote SV40 DNA sequences. Cell, 1981,27(2 Pt 1):299-308. [DOI]
[2]	Blackwood EM, Kadonaga JT . Going the distance: a current view of enhancer action. Science, 1998,281(5373):60-63. [DOI]
[3]	Bulger M, Groudine M . Functional and mechanistic diversity of distal transcription enhancers. Cell, 2011,144(3):327-339. [DOI]
[4]	Sun CB, Zhang X . Advance in the research on super- enhancer. Hereditas(Beijing), 2016,38(12):1056-1068.
[4]	孙长斌, 张曦 . 超级增强子研究进展. 遗传, 2016,38(12):1056-1068. [DOI]
[5]	Levine M . Transcriptional enhancers in animal development and evolution. Curr Biol, 2010,20(17):R754-763. [DOI]
[6]	Sengupta S, George RE . Super-enhancer-driven transcriptional dependencies in cancer. Trends Cancer, 2017,3(4):269-281. [DOI]
[7]	Ing-Simmons E, Seitan VC, Faure AJ, Flicek P, Carroll T, Dekker J, Fisher AG, Lenhard B, Merkenschlager M . Spatial enhancer clustering and regulation of enhancer- proximal genes by cohesin. Genome Res, 2015,25(4):504-513. [DOI]
[8]	Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, Rahl PB, Lee TI, Young RA . Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell, 2013,153(2):307-319. [DOI]
[9]	Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-Andre V, Sigova AA, Hoke HA, Young RA . Super-enhancers in the control of cell identity and disease. Cell, 2013,155(4):934-947. [DOI]
[10]	Christensen CL, Kwiatkowski N, Abraham BJ, Carretero J, Al-Shahrour F, Zhang T, Chipumuro E, Herter-Sprie GS, Akbay EA, Altabef A, Zhang J, Shimamura T, Capelletti M, Reibel JB, Cavanaugh JD, Gao P, Liu Y, Michaelsen SR, Poulsen HS, Aref AR, Barbie DA, Bradner JE, George RE, Gray NS, Young RA, Wong KK . Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor. Cancer Cell, 2014,26(6):909-922. [DOI]
[11]	Hnisz D, Schuijers J, Lin CY, Weintraub AS, Abraham BJ, Lee TI, Bradner JE, Young RA . Convergence of developmental and oncogenic signaling pathways at transcriptional super-enhancers. Mol Cell, 2015,58(2):362-370. [DOI]
[12]	Saint-André V, Federation AJ, Lin CY, Abraham BJ, Reddy J, Lee TI, Bradner JE, Young RA . Models of human core transcriptional regulatory circuitries. Genome Res, 2016,26(3):385-396. [DOI]
[13]	Drier Y, Cotton MJ, Williamson KE, Gillespie SM, Ryan RJ, Kluk MJ, Carey CD, Rodig SJ, Sholl LM, Afrogheh AH, Faquin WC, Queimado L, Qi J, Wick MJ, El-Naggar AK, Bradner JE, Moskaluk CA, Aster JC, Knoechel B, Bernstein BE . An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma. Nat Genet, 2016,48(3):265-272. [DOI]
[14]	Adam RC, Fuchs E . The Yin and Yang of chromatin dynamics in stem cell fate selection. Trends Genet, 2016,32(2):89-100. [DOI]
[15]	Kaufman CK, Mosimann C, Fan ZP, Yang S, Thomas AJ, Ablain J, Tan JL, Fogley RD, van Rooijen E, Hagedorn EJ, Ciarlo C, White RM, Matos DA, Puller AC, Santoriello C, Liao EC, Young RA, Zon LI . A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation. Science, 2016, 351(6272): aad2197. [DOI]
[16]	Witte S, Bradley A, Enright AJ, Muljo SA . High-density P300 enhancers control cell state transitions. BMC Genomics, 2015,16:903. [DOI]
[17]	Lovén J, Hoke HA, Lin CY, Lau A, Orlando DA, Vakoc CR, Bradner JE, Lee TI, Young RA . Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell, 2013,153(2):320-334. [DOI]
[18]	Chapuy B, McKeown MR, Lin CY, Monti S, Roemer MG, Qi J, Rahl PB, Sun HH, Yeda KT, Doench JG, Reichert E, Kung AL, Rodig SJ, Young RA, Shipp MA, Bradner JE . Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. Cancer Cell, 2013,24(6):777-790. [DOI]
[19]	Herranz D, Ambesi-Impiombato A, Palomero T, Schnell SA, Belver L, Wendorff AA, Xu L, Castillo-Martin M, Llobet-Navás D, Cordon-Cardo C, Clappier E, Soulier J, Ferrando AA . A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia. Nat Med, 2014,20(10):1130-1137. [DOI]
[20]	Mansour MR, Abraham BJ, Anders L, Berezovskaya A, Gutierrez A, Durbin AD, Etchin J, Lawton L, Sallan SE, Silverman LB, Loh ML, Hunger SP, Sanda T, Young RA, Look AT . Oncogene regulation. An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element. Science, 2014,346(6215):1373-1377. [DOI]
[21]	Sengupta D, Kannan A, Kern M, Moreno MA, Vural E, Stack B, J r., Suen JY, Tackett AJ, Gao L . Disruption of BRD4 at H3K27Ac-enriched enhancer region correlates with decreased c-Myc expression in Merkel cell carcinoma. Epigenetics, 2015,10(6):460-466. [DOI]
[22]	Pelish HE, Liau BB, Nitulescu II, Tangpeerachaikul A, Poss ZC, Da Silva DH, Caruso BT, Arefolov A, Fadeyi O, Christie AL, Du K, Banka D, Schneider EV, Jestel A, Zou G, Si C, Ebmeier CC, Bronson RT, Krivtsov AV, Myers AG, Kohl NE, Kung AL, Armstrong SA, Lemieux ME, Taatjes DJ, Shair MD . Mediator kinase inhibition further activates super-enhancer-associated genes in AML. Nature, 2015,526(7572):273-276. [DOI]
[23]	Johnatty SE, Tyrer JP, Kar S, Beesley J, Lu Y, Gao B, Fasching PA, Hein A, Ekici AB, Beckmann MW, Lambrechts D, Van Nieuwenhuysen E, Vergote I, Lambrechts S, Rossing MA, Doherty JA, Chang-Claude J, Modugno F, Ness RB, Moysich KB, Levine DA, Kiemeney LA, Massuger LF, Gronwald J, Lubinski J, Jakubowska A, Cybulski C, Brinton L, Lissowska J, Wentzensen N, Song H, Rhenius V, Campbell I, Eccles D, Sieh W, Whittemore AS, McGuire V, Rothstein JH, Sutphen R, Anton-Culver H, Ziogas A, Gayther SA, Gentry-Maharaj A, Menon U, Ramus SJ, Pearce CL, Pike MC, Stram DO, Wu AH, Kupryjanczyk J, Dansonka- Mieszkowska A, Rzepecka IK, Spiewankiewicz B, Goodman MT, Wilkens LR, Carney ME, Thompson PJ, Heitz F, du Bois A, Schwaab I, Harter P, Pisterer J, Hillemanns P, Group AGOS, Karlan BY, Walsh C, Lester J, Orsulic S, Winham SJ, Earp M, Larson MC, Fogarty ZC, Hogdall E, Jensen A, Kjaer SK, Fridley BL, Cunningham JM, Vierkant RA, Schildkraut JM, Iversen ES, Terry KL, Cramer DW, Bandera EV, Orlow I, Pejovic T, Bean Y, Hogdall C, Lundvall L, McNeish I, Paul J, Carty K, Siddiqui N, Glasspool R, Sellers T, Kennedy C, Chiew YE, Berchuck A, MacGregor S, Pharoah PD, Goode EL, deFazio A, Webb PM, Chenevix-Trench G , Australian Ovarian Cancer Study G. Genome-wide analysis identifies novel loci associated with ovarian cancer outcomes: findings from the ovarian cancer association consortium. Clin Cancer Res, 2015,21(23):5264-5276. [DOI]
[24]	Zhang X, Choi PS, Francis JM, Imielinski M, Watanabe H, Cherniack AD, Meyerson M . Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers. Nat Genet, 2016,48(2):176-182. [DOI]
[25]	Yang H, Schramek D, Adam RC, Keyes BE, Wang P, Zheng D, Fuchs E . ETS family transcriptional regulators drive chromatin dynamics and malignancy in squamous cell carcinomas. eLife, 2015,4:e10870. [DOI]
[26]	Wang Y, Zhang T, Kwiatkowski N, Abraham BJ, Lee TI, Xie S, Yuzugullu H, Von T, Li H, Lin Z, Stover DG, Lim E, Wang ZC, Iglehart JD, Young RA, Gray NS, Zhao JJ . CDK7-dependent transcriptional addiction in triple-negative breast cancer. Cell, 2015,163(1):174-186. [DOI]
[27]	Jiang YY, Lin DC, Mayakonda A, Hazawa M, Ding LW, Chien WW, Xu L, Chen Y, Xiao JF, Senapedis W, Baloglu E, Kanojia D, Shang L, Xu X, Yang H, Tyner JW, Wang MR, Koeffler HP . Targeting super-enhancer-associated oncogenes in oesophageal squamous cell carcinoma. Gut, 2017,66(8):1358-1368. [DOI]
[28]	Togel L, Nightingale R, Chueh AC, Jayachandran A, Tran H, Phesse T, Wu R, Sieber OM, Arango D, Dhillon AS, Dawson MA, Diez-Dacal B, Gahman TC, Filippakopoulos P, Shiau AK, Mariadason JM . Dual targeting of bromodomain and extraterminal domain proteins, and WNT or MAPK signaling, inhibits c-MYC expression and proliferation of colorectal cancer cells. Mol Cancer Ther, 2016,15(6):1217-1226. [DOI]
[29]	Hanahan D, Weinberg RA . The hallmarks of cancer. Cell, 2000, 100(1):57-70. [DOI]
[30]	Hanahan D, Weinberg RA . Hallmarks of cancer: the next generation. Cell, 2011,144(5):646-674. [DOI]
[31]	Suzuki HI, Young RA, Sharp PA . Super-enhancer- mediated RNA processing revealed by integrative microRNA network analysis. Cell, 2017,168(6):1000-1014 e15. [DOI]
[32]	Xie JJ, Jiang YY, Jiang Y, Li CQ, Chee LM, An O, Mayakonda A, Ding LW, Long L, Sun C, Lin LH, Chen L, Wu JY, Wu ZY, Cao Q, Fang WK, Yang W, Meltzer SJ, Yang H, Fullwood M, Xu LY, Li EM, Lin DC, Koeffler HP . Super-enhancer-driven long non-coding RNA LINC01503, regulated by TP63, is over-expressedand oncogenic in squamous cell carcinoma. Gastroenterology, 2018, 154(8): 2137- 2151.e1. [DOI]
[33]	Jiao W, Chen Y, Song H, Li D, Mei H, Yang F, Fang E, Wang X, Huang K, Zheng L, Tong Q . HPSE enhancer RNA promotes cancer progression through driving chromatin looping and regulating hnRNPU/p300/EGR1/HPSE axis. Oncogene, 2018,37(20):2728-2745. [DOI]
[34]	Cheng X, Yang Q, Tan ZD, Tan Y, Pu H, Zhao X, Zhang SH, Zhu L . The current research status of enhancer RNAs. Hereditas(Beijing), 2017,39(9):784-797.
[34]	程霄, 杨琼, 谭镇东, 谭娅, 蒲红州, 赵雪, 张顺华, 朱砺 . 增强子RNA研究现状. 遗传, 2017,39(9):784-797. [DOI]
[35]	Lin CY, Erkek S, Tong Y, Yin L, Federation AJ, Zapatka M, Haldipur P, Kawauchi D, Risch T, Warnatz HJ, Worst BC, Ju B, Orr BA, Zeid R, Polaski DR, Segura-Wang M, Waszak SM, Jones DT, Kool M, Hovestadt V, Buchhalter I, Sieber L, Johann P, Chavez L, Groschel S, Ryzhova M, Korshunov A, Chen W, Chizhikov VV, Millen KJ, Amstislavskiy V, Lehrach H, Yaspo ML, Eils R, Lichter P, Korbel JO, Pfister SM, Bradner JE, Northcott PA . Active medulloblastoma enhancers reveal subgroup-specific cellular origins. Nature, 2016,530(7588):57-62. [DOI]
[36]	Oldridge DA, Wood AC, Weichert-Leahey N, Crimmins I, Sussman R, Winter C, McDaniel LD, Diamond M, Hart LS, Zhu S, Durbin AD, Abraham BJ, Anders L, Tian L, Zhang S, Wei JS, Khan J, Bramlett K, Rahman N, Capasso M, Iolascon A, Gerhard DS, Guidry Auvil JM, Young RA, Hakonarson H,Diskin SJ, Look AT, Maris JM . Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism. Nature, 2015,528(7582):418-421. [DOI]
[37]	Super-enhancers facilitate gene regulation by signaling pathways. Cancer Discov, 2015, 5(5): OF11. [DOI]
[38]	Nabet B, P óB, Reyes JM, Shieh K, Lin CY, Will CM, Popovic R, Ezponda T, Bradner JE, Golden AA, Licht JD . Deregulation of the ras-erk signaling axis modulates the enhancer landscape. Cell Rep, 2015,12(8):1300-1313. [DOI]
[39]	Adelman K, Lis JT . Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans. Nat Rev Genet, 2012,13(10):720-731. [DOI]
[40]	Galli GG, Carrara M, Yuan WC, Valdes-Quezada C, Gurung B, Pepe-Mooney B, Zhang T, Geeven G, Gray NS, de Laat W, Calogero RA, Camargo FD . YAP drives growth by controlling transcriptional pause release from dynamic enhancers. Mol Cell, 2015,60(2):328-337. [DOI]
[41]	Yimlamai D, Fowl BH, Camargo FD . Emerging evidence on the role of the Hippo/YAP pathway in liver physiology and cancer. J Hepatol, 2015,63(6):1491-1501. [DOI]
[42]	Wang H, Zang C, Taing L, Arnett KL, Wong YJ, Pear WS, Blacklow SC, Liu XS, Aster JC . NOTCH1-RBPJ complexes drive target gene expression through dynamic interactions with superenhancers. Proc Natl Acad Sci USA, 2014,111(2):705-710. [DOI]
[43]	Sur I, Taipale J . The role of enhancers in cancer. Nat Rev Cancer, 2016,16(8):483-493. [DOI]
[44]	Vaharautio A, Taipale J . Cancer. Cancer by super-enhancer. Science, 2014,346(6215):1291-1292. [DOI]
[45]	Lin CY, Loven J, Rahl PB, Paranal RM, Burge CB, Bradner JE, Lee TI, Young RA . Transcriptional amplification in tumor cells with elevated c-Myc. Cell, 2012,151(1):56-67. [DOI]
[46]	Didiasova M, Schaefer L, Wygrecka M . Targeting GLI transcription factors in cancer. Molecules, 2018,23(5):1003. [DOI]
[47]	Nilson KA, Guo J, Turek ME, Brogie JE, Delaney E, Luse DS, Price DH . THZ1 reveals roles for Cdk7 in co-transcriptional capping and pausing. Mol Cell, 2015,59(4):576-587. [DOI]
[48]	Di Micco R, Fontanals-Cirera B, Low V, Ntziachristos P, Yuen SK, Lovell CD, Dolgalev I, Yonekubo Y, Zhang G, Rusinova E, Gerona-Navarro G, Canamero M, Ohlmeyer M, Aifantis I, Zhou MM, Tsirigos A, Hernando E . Control of embryonic stem cell identity by BRD4-dependent transcriptional elongation of super-enhancer-associated pluripotency genes. Cell Rep, 2014,9(1):234-247. [DOI]
[49]	Bartkowiak B, Liu P, Phatnani HP, Fuda NJ, Cooper JJ, Price DH, Adelman K, Lis JT, Greenleaf AL . CDK12 is a transcription elongation-associated CTD kinase, the metazoan ortholog of yeast Ctk1. Genes Dev, 2010,24(20):2303-2316. [DOI]
[50]	Liang K, Gao X, Gilmore JM, Florens L, Washburn MP, Smith E, Shilatifard A . Characterization of human cyclin- dependent kinase 12 (CDK12) and CDK13 complexes in C-terminal domain phosphorylation, gene transcription, and RNA processing. Mol Cell Biol, 2015,35(6):928-938. [DOI]
[51]	Shin HY . Targeting super-enhancers for disease treatment and diagnosis. Mol Cells, 2018,41(6):506-514. [DOI]
[52]	Bai L, Zhou B, Yang CY, Ji J, McEachern D, Przybranowski S, Jiang H, Hu J, Xu F, Zhao Y, Liu L, Fernandez-Salas E, Xu J, Dou Y, Wen B, Sun D, Meagher J, Stuckey J, Hayes DF, Li S, Ellis MJ, Wang S . Targeted degradation of BET proteins in triple-negative breast cancer. Cancer Res, 2017,77(9):2476-2487. [DOI]
[53]	Odore E, Lokiec F, Cvitkovic E, Bekradda M, Herait P, Bourdel F, Kahatt C, Raffoux E, Stathis A, Thieblemont C, Quesnel B, Cunningham D, Riveiro ME, Rezai K . Phase I population pharmacokinetic assessment of the oral bromodomain inhibitor OTX015 in patients with haematologic malignancies. Clinical Pharmacokinetics, 2016,3(55):397-405. [DOI]
[54]	Berthon C, Raffoux E, Thomas X, Vey N, Gomez-Roca C, Yee K, Taussig DC, Rezai K, Roumier C, Herait P, Kahatt C, Quesnel B, Michallet M, Recher C, Lokiec F, Preudhomme C, Dombret H . Bromodomain inhibitor OTX015 in patients with acute leukaemia: a dose- escalation, phase 1 study. The Lancet Haematology, 2016,3(4):186-195. [DOI]
[55]	Chipumuro E, Marco E, Christensen CL, Kwiatkowski N, Zhang T, Hatheway CM, Abraham BJ, Sharma B, Yeung C, Altabef A, Perez-Atayde A, Wong KK, Yuan GC, Gray NS, Young RA, George RE . CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN- driven cancer. Cell, 2014,159(5):1126-1139. [DOI]
[56]	Wong RWJ, Ngoc PCT, Leong WZ, Yam AWY, Zhang T, Asamitsu K, Iida S, Okamoto T, Ueda R, Gray NS, Ishida T, Sanda T . Enhancer profiling identifies critical cancer genes and characterizes cell identity in adult T-cell leukemia. Blood, 2017,130(21):2326-2338. [DOI]
[57]	Zhang T, Kwiatkowski N, Olson CM, Dixon-Clarke SE, Abraham BJ, Greifenberg AK, Ficarro SB, Elkins JM, Liang Y, Hannett NM, Manz T, Hao M, Bartkowiak B, Greenleaf AL, Marto JA, Geyer M, Bullock AN, Young RA, Gray NS . Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors. Nat Chem Biol, 2016,12(10):876-884. [DOI]
[58]	Kennedy AL, Vallurupalli M, Chen L, Crompton B, Cowley G, Vazquez F, Weir BA, Tsherniak A, Parasuraman S, Kim S, Alexe G, Stegmaier K . Functional, chemical genomic, and super-enhancer screening identify sensitivity to cyclin D1/CDK4 pathway inhibition in Ewing sarcoma. Oncotarget, 2015,6(30):30178-30193. [DOI]
[59]	Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, Kastritis E, Gilpatrick T, Paranal RM, Qi J, Chesi M, Schinzel AC, McKeown MR, Heffernan TP, Vakoc CR, Bergsagel PL, Ghobrial IM, Richardson PG, Young RA, Hahn WC, Anderson KC, Kung AL, Bradner JE, Mitsiades CS . BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell, 2011,146(6):904-917. [DOI]
[60]	Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, Philpott M, Munro S, McKeown MR, Wang Y, Christie AL, West N, Cameron MJ, Schwartz B, Heightman TD, La Thangue N, French CA, Wiest O, Kung AL, Knapp S, Bradner JE . Selective inhibition of BET bromodomains. Nature, 2010,468(7327):1067-1073. [DOI]
[61]	Amorim S, Stathis A, Gleeson M, Iyengar S, Magarotto V, Leleu X, Morschhauser F, Karlin L, Broussais F, Rezai K, Herait P, Kahatt C, Lokiec F, Salles G, Facon T, Palumbo A, Cunningham D, Zucca E, Thieblemont C . Bromodomain inhibitor OTX015 in patients with lymphoma or multiple myeloma: a dose-escalation, open-label, pharmacokinetic, phase 1 study. Lancet Haematol, 2016,3(4):e196-204. [DOI]
[62]	Winter GE, Buckley DL, Paulk J, Roberts JM, Souza A, Dhe-Paganon S, Bradner JE. DRUG DEVELOPMENT . Phthalimide conjugation as a strategy for in vivo target protein degradation. Science, 2015,348(6241):1376-1381. [DOI]
[63]	Tasdemir N, Banito A, Roe JS, Alonso-Curbelo D, Camiolo M, Tschaharganeh DF, Huang CH, Aksoy O, Bolden JE, Chen CC, Fennell M, Thapar V, Chicas A, Vakoc CR, Lowe SW . BRD4 connects enhancer remodeling to senescence immune surveillance. Cancer Discov, 2016,6(6):612-629. [DOI]
[64]	Kwiatkowski N, Zhang T, Rahl PB, Abraham BJ, Reddy J, Ficarro SB, Dastur A, Amzallag A, Ramaswamy S, Tesar B, Jenkins CE, Hannett NM, McMillin D, Sanda T, Sim T, Kim ND, Look T, Mitsiades CS, Weng AP, Brown JR, Benes CH, Marto JA, Young RA, Gray NS . Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature, 2014,511(7511):616-620. [DOI]

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

超级增强子在肿瘤研究中的进展

Research progress of super enhancer in cancer

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	张競文,续倩,李国亮. 癌症发生发展中的表观遗传学研究[J]. 遗传, 2019, 41(7): 567-581.
[2]	郑晓飞,黄海燕,吴强. 染色质架构蛋白CTCF调控UGT1基因簇的表达[J]. 遗传, 2019, 41(6): 509-523.
[3]	刘振宁, 袁黎, VenkatesanSundaresan, 余小林. 拟南芥CKI1基因上游转录调控因子筛选及鉴定[J]. 遗传, 2019, 41(5): 430-438.
[4]	孙兆庆, 闫波. 转录因子GATA6在心血管疾病中的作用及其调控机制[J]. 遗传, 2019, 41(5): 375-383.
[5]	刘玄石, 李巍. 早产相关基因的挖掘与特征分析[J]. 遗传, 2019, 41(5): 413-421.
[6]	孙晓伟,李宏阳,王健,程博. PRC1.6复合体表观遗传调控生殖谱系特异性基因的时空表达[J]. 遗传, 2019, 41(4): 271-284.
[7]	石田培,张莉. 全转录组学在畜牧业中的应用[J]. 遗传, 2019, 41(3): 193-205.
[8]	于好强,孙福艾,冯文奇,路风中,李晚忱,付凤玲. 转录因子BES1/BZR1调控植物生长发育及抗逆性[J]. 遗传, 2019, 41(3): 206-214.
[9]	张高华, 于树涛, 王鹤, 王旭达. 高油酸花生发芽期低温胁迫转录组及差异表达基因分析[J]. 遗传, 2019, 41(11): 1050-1059.
[10]	刘启鹏, 安妮, 岑山, 李晓宇. piRNA抑制基因转座的分子机制[J]. 遗传, 2018, 40(6): 445-450.
[11]	鞠君毅,赵权. γ-珠蛋白基因表达调控机制与临床应用[J]. 遗传, 2018, 40(6): 429-444.
[12]	丁庆倩,王小婷,胡利琴,齐欣,葛林豪,徐伟亚,徐兆师,周永斌,贾冠清,刁现民,闵东红,马有志,陈明. 谷子MYB类转录因子SiMYB42提高转基因拟南芥低氮胁迫耐性[J]. 遗传, 2018, 40(4): 327-338.
[13]	禚建树, 荆晓燕, 杜欣, 杨秀芹. 哺乳动物嵌合RNAs产生机制：cis-SAGe[J]. 遗传, 2018, 40(2): 145-154.
[14]	任岚,肖茹丹,张倩,娄晓敏,张昭军,方向东. KLF1和KLF9对K562细胞红系分化的协同调控作用[J]. 遗传, 2018, 40(11): 998-1006.
[15]	杨莹,陈宇晟,孙宝发,杨运桂. RNA甲基化修饰调控和规律[J]. 遗传, 2018, 40(11): 964-976.