A global analysis of the complex landscape of isoforms and regulatory networks of p63 in human cells and tissues

. 2015 Aug 07 ; 16 () : 584. [epub] 20150807

Jazyk angličtina Země Velká Británie, Anglie Médium electronic

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid26251276

Grantová podpora
R03 HD073891 NICHD NIH HHS - United States
R21 DE021137 NIDCR NIH HHS - United States
R03HD073891 NICHD NIH HHS - United States
R21DE021137 NIDCR NIH HHS - United States

Odkazy

PubMed 26251276
PubMed Central PMC4528692
DOI 10.1186/s12864-015-1793-9
PII: 10.1186/s12864-015-1793-9
Knihovny.cz E-zdroje

BACKGROUND: The transcription factor p63 belongs to the p53/p63/p73 family and plays key functional roles during normal epithelial development and differentiation and in pathological states such as squamous cell carcinomas. The human TP63 gene, located on chromosome 3q28 is driven by two promoters that generate the full-length transactivating (TA) and N-terminal truncated (ΔN) isoforms. Furthermore alternative splicing at the C-terminus gives rise to additional α, β, γ and likely several other minor variants. Teasing out the expression and biological function of each p63 variant has been both the focus of, and a cause for contention in the p63 field. RESULTS: Here we have taken advantage of a burgeoning RNA-Seq based genomic data-sets to examine the global expression profiles of p63 isoforms across commonly utilized human cell-lines and major tissues and organs. Consistent with earlier studies, we find ΔNp63 transcripts, primarily that of the ΔNp63α isoforms, to be expressed in most cells of epithelial origin such as those of skin and oral tissues, mammary glands and squamous cell carcinomas. In contrast, TAp63 is not expressed in the majority of normal cell-types and tissues; rather it is selectively expressed at moderate to high levels in a subset of Burkitt's and diffuse large B-cell lymphoma cell lines. We verify this differential expression pattern of p63 isoforms by Western blot analysis, using newly developed ΔN and TA specific antibodies. Furthermore using unsupervised clustering of human cell lines, tissues and organs, we show that ΔNp63 and TAp63 driven transcriptional networks involve very distinct sets of molecular players, which may underlie their different biological functions. CONCLUSIONS: In this study we report comprehensive and global expression profiles of p63 isoforms and their relationship to p53/p73 and other potential transcriptional co-regulators. We curate publicly available data generated in part by consortiums such as ENCODE, FANTOM and Human Protein Atlas to delineate the vastly different transcriptomic landscapes of ΔNp63 and TAp63. Our studies help not only in dispelling prevailing myths and controversies on p63 expression in commonly used human cell lines but also augur new isoform- and cell type-specific activities of p63.

Zobrazit více v PubMed

Lemon B, Tjian R. Orchestrated response: a symphony of transcription factors for gene control. Genes Dev. 2000;14(20):2551–2569. doi: 10.1101/gad.831000. PubMed DOI

Kornblihtt AR. Promoter usage and alternative splicing. Curr Opin Cell Biol. 2005;17(3):262–268. doi: 10.1016/j.ceb.2005.04.014. PubMed DOI

Murray-Zmijewski F, Lane DP, Bourdon JC. p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress. Cell Death Differ. 2006;13(6):962–972. doi: 10.1038/sj.cdd.4401914. PubMed DOI

Candi E, Agostini M, Melino G, Bernassola F. How the TP53 family proteins TP63 and TP73 contribute to tumorigenesis: regulators and effectors. Hum Mutat. 2014;35(6):702–714. doi: 10.1002/humu.22523. PubMed DOI

Costanzo A, Pediconi N, Narcisi A, Guerrieri F, Belloni L, Fausti F, Botti E, Levrero M. TP63 and TP73 in cancer, an unresolved “family” puzzle of complexity, redundancy and hierarchy. FEBS Lett. 2014;588(16):2590–2599. doi: 10.1016/j.febslet.2014.06.047. PubMed DOI

Khoury MP, Bourdon JC. p53 Isoforms: An Intracellular Microprocessor? Genes Cancer. 2011;2(4):453–465. doi: 10.1177/1947601911408893. PubMed DOI PMC

Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dotsch V, Andrews NC, Caput D, McKeon F. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell. 1998;2(3):305–316. doi: 10.1016/S1097-2765(00)80275-0. PubMed DOI

Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR, Bradley A. p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature. 1999;398(6729):708–713. doi: 10.1038/19531. PubMed DOI

Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C, et al. p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature. 1999;398(6729):714–718. doi: 10.1038/19539. PubMed DOI

Koster MI, Kim S, Mills AA, DeMayo FJ, Roop DR. p63 is the molecular switch for initiation of an epithelial stratification program. Genes Dev. 2004;18(2):126–131. doi: 10.1101/gad.1165104. PubMed DOI PMC

Candi E, Cipollone R, Rivetti di Val Cervo P, Gonfloni S, Melino G, Knight R. p63 in epithelial development. Cell Mol Life Sci. 2008;65(20):3126–3133. doi: 10.1007/s00018-008-8119-x. PubMed DOI PMC

Botchkarev VA, Flores ER: p53/p63/p73 in the epidermis in health and disease. Cold Spring Harb Perspect Med 2014, 4(8): doi:10.1101/cshperspect.a015248 PubMed PMC

Brandt T, Petrovich M, Joerger AC, Veprintsev DB. Conservation of DNA-binding specificity and oligomerisation properties within the p53 family. BMC Genomics. 2009;10:628. doi: 10.1186/1471-2164-10-628. PubMed DOI PMC

Joerger AC, Rajagopalan S, Natan E, Veprintsev DB, Robinson CV, Fersht AR. Structural evolution of p53, p63, and p73: Implication for heterotetramer formation. Proc Natl Acad Sci U S A. 2009;106(42):17705–17710. doi: 10.1073/pnas.0905867106. PubMed DOI PMC

Suh EK, Yang A, Kettenbach A, Bamberger C, Michaelis AH, Zhu Z, Elvin JA, Bronson RT, Crum CP, McKeon F. p63 protects the female germ line during meiotic arrest. Nature. 2006;444(7119):624–628. doi: 10.1038/nature05337. PubMed DOI

Su X, Paris M, Gi YJ, Tsai KY, Cho MS, Lin YL, Biernaskie JA, Sinha S, Prives C, Pevny LH, et al. TAp63 prevents premature aging by promoting adult stem cell maintenance. Cell Stem Cell. 2009;5(1):64–75. doi: 10.1016/j.stem.2009.04.003. PubMed DOI PMC

Romano RA, Smalley K, Magraw C, Serna VA, Kurita T, Raghavan S, Sinha S. DeltaNp63 knockout mice reveal its indispensable role as a master regulator of epithelial development and differentiation. Development. 2012;139(4):772–782. doi: 10.1242/dev.071191. PubMed DOI PMC

Pignon JC, Grisanzio C, Geng Y, Song J, Shivdasani RA, Signoretti S. p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia. Proc Natl Acad Sci U S A. 2013;110(20):8105–8110. doi: 10.1073/pnas.1221216110. PubMed DOI PMC

Chakravarti D, Su X, Cho MS, Bui NH, Coarfa C, Venkatanarayan A, Benham AL, Flores Gonzalez RE, Alana J, Xiao W, et al. Induced multipotency in adult keratinocytes through down-regulation of DeltaNp63 or DGCR8. Proc Natl Acad Sci U S A. 2014;111(5):E572–581. doi: 10.1073/pnas.1319743111. PubMed DOI PMC

Guo X, Keyes WM, Papazoglu C, Zuber J, Li W, Lowe SW, Vogel H, Mills AA. TAp63 induces senescence and suppresses tumorigenesis in vivo. Nat Cell Biol. 2009;11(12):1451–1457. doi: 10.1038/ncb1988. PubMed DOI PMC

Rizzo JM, Romano RA, Bard J, Sinha S. RNA-seq Studies Reveal New Insights into p63 and the Transcriptomic Landscape of the Mouse Skin. J Invest Dermatol. 2015;135(2):629–632. doi: 10.1038/jid.2014.384. PubMed DOI

Romano RA, Ortt K, Birkaya B, Smalley K, Sinha S. An active role of the DeltaN isoform of p63 in regulating basal keratin genes K5 and K14 and directing epidermal cell fate. PLoS One. 2009;4(5):e5623. doi: 10.1371/journal.pone.0005623. PubMed DOI PMC

Hu L, Liu J, Li Z, Ozturk F, Gurumurthy C, Romano RA, Sinha S, Nawshad A. TGFbeta3 Regulates Periderm Removal through DeltaNp63 in the Developing Palate. J Cell Physiol. 2015;230:1212–25. doi: 10.1002/jcp.24856. PubMed DOI

Crum CP, McKeon FD. p63 in epithelial survival, germ cell surveillance, and neoplasia. Annu Rev Pathol. 2010;5:349–371. doi: 10.1146/annurev-pathol-121808-102117. PubMed DOI

Candi E, Dinsdale D, Rufini A, Salomoni P, Knight RA, Mueller M, Krammer PH, Melino G. TAp63 and DeltaNp63 in cancer and epidermal development. Cell Cycle. 2007;6(3):274–285. doi: 10.4161/cc.6.3.3797. PubMed DOI

Koster MI, Dai D, Roop DR. Conflicting roles for p63 in skin development and carcinogenesis. Cell Cycle. 2007;6(3):269–273. doi: 10.4161/cc.6.3.3792. PubMed DOI

Su X, Gi YJ, Chakravarti D, Chan IL, Zhang A, Xia X, Tsai KY, Flores ER. TAp63 is a master transcriptional regulator of lipid and glucose metabolism. Cell Metab. 2012;16(4):511–525. doi: 10.1016/j.cmet.2012.09.006. PubMed DOI PMC

Su X, Chakravarti D, Flores ER. p63 steps into the limelight: crucial roles in the suppression of tumorigenesis and metastasis. Nat Rev Cancer. 2013;13(2):136–143. doi: 10.1038/nrc3446. PubMed DOI PMC

Ramsey MR, Wilson C, Ory B, Rothenberg SM, Faquin W, Mills AA, Ellisen LW. FGFR2 signaling underlies p63 oncogenic function in squamous cell carcinoma. J Clin Invest. 2013;123(8):3525–3538. doi: 10.1172/JCI68899. PubMed DOI PMC

Chakrabarti R, Wei Y, Hwang J, Hang X, Andres Blanco M, Choudhury A, Tiede B, Romano RA, DeCoste C, Mercatali L, et al. DeltaNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling. Nat Cell Biol. 2014;16(10):1004–1015. doi: 10.1038/ncb3040. PubMed DOI PMC

Su X, Chakravarti D, Cho MS, Liu L, Gi YJ, Lin YL, Leung ML, El-Naggar A, Creighton CJ, Suraokar MB, et al. TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature. 2010;467(7318):986–990. doi: 10.1038/nature09459. PubMed DOI PMC

Rosenbluth JM, Johnson K, Tang L, Triplett T, Pietenpol JA. Evaluation of p63 and p73 antibodies for cross-reactivity. Cell Cycle. 2009;8(22):3702–3706. doi: 10.4161/cc.8.22.10036. PubMed DOI

Myers RM, Stamatoyannopoulos J, Snyder M, Dunham I, Hardison RC, Bernstein BE, Gingeras TR, Kent WJ, Birney E, Wold B, et al. A user’s guide to the encyclopedia of DNA elements (ENCODE) PLoS Biol. 2011;9(4):e1001046. doi: 10.1371/journal.pbio.1001046. PubMed DOI PMC

Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, Pimentel H, Salzberg SL, Rinn JL, Pachter L. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc. 2012;7(3):562–578. doi: 10.1038/nprot.2012.016. PubMed DOI PMC

Li B, Dewey CN. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC bioinformatics. 2011;12:323. doi: 10.1186/1471-2105-12-323. PubMed DOI PMC

Neilsen PM, Noll JE, Suetani RJ, Schulz RB, Al-Ejeh F, Evdokiou A, Lane DP, Callen DF. Mutant p53 uses p63 as a molecular chaperone to alter gene expression and induce a pro-invasive secretome. Oncotarget. 2011;2(12):1203–1217. doi: 10.18632/oncotarget.382. PubMed DOI PMC

Adorno M, Cordenonsi M, Montagner M, Dupont S, Wong C, Hann B, Solari A, Bobisse S, Rondina MB, Guzzardo V, et al. A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis. Cell. 2009;137(1):87–98. doi: 10.1016/j.cell.2009.01.039. PubMed DOI

Strano S, Fontemaggi G, Costanzo A, Rizzo MG, Monti O, Baccarini A, Del Sal G, Levrero M, Sacchi A, Oren M, et al. Physical interaction with human tumor-derived p53 mutants inhibits p63 activities. J Biol Chem. 2002;277(21):18817–18826. doi: 10.1074/jbc.M201405200. PubMed DOI

Muller PA, Trinidad AG, Caswell PT, Norman JC, Vousden KH. Mutant p53 regulates Dicer through p63-dependent and -independent mechanisms to promote an invasive phenotype. J Biol Chem. 2014;289(1):122–132. doi: 10.1074/jbc.M113.502138. PubMed DOI PMC

Muller PA, Caswell PT, Doyle B, Iwanicki MP, Tan EH, Karim S, Lukashchuk N, Gillespie DA, Ludwig RL, Gosselin P, et al. Mutant p53 drives invasion by promoting integrin recycling. Cell. 2009;139(7):1327–1341. doi: 10.1016/j.cell.2009.11.026. PubMed DOI

Caserta TM, Kommagani R, Yuan Z, Robbins DJ, Mercer CA, Kadakia MP. p63 overexpression induces the expression of Sonic Hedgehog. Mol Cancer Res. 2006;4(10):759–768. doi: 10.1158/1541-7786.MCR-05-0149. PubMed DOI

Truong AB, Kretz M, Ridky TW, Kimmel R, Khavari PA. p63 regulates proliferation and differentiation of developmentally mature keratinocytes. Genes Dev. 2006;20(22):3185–3197. doi: 10.1101/gad.1463206. PubMed DOI PMC

Ichikawa T, Suenaga Y, Koda T, Ozaki T, Nakagawara A. TAp63-dependent induction of growth differentiation factor 15 (GDF15) plays a critical role in the regulation of keratinocyte differentiation. Oncogene. 2008;27(4):409–420. doi: 10.1038/sj.onc.1210658. PubMed DOI

Kretz M, Webster DE, Flockhart RJ, Lee CS, Zehnder A, Lopez-Pajares V, Qu K, Zheng GX, Chow J, Kim GE, et al. Suppression of progenitor differentiation requires the long noncoding RNA ANCR. Genes Dev. 2012;26(4):338–343. doi: 10.1101/gad.182121.111. PubMed DOI PMC

Shen J, van den Bogaard EH, Kouwenhoven EN, Bykov VJ, Rinne T, Zhang Q, Tjabringa GS, Gilissen C, van Heeringen SJ, Schalkwijk J, et al. APR-246/PRIMA-1(MET) rescues epidermal differentiation in skin keratinocytes derived from EEC syndrome patients with p63 mutations. Proc Natl Acad Sci U S A. 2013;110(6):2157–2162. doi: 10.1073/pnas.1201993110. PubMed DOI PMC

Ozsolak F, Milos PM. RNA sequencing: advances, challenges and opportunities. Nat Rev Genet. 2011;12(2):87–98. doi: 10.1038/nrg2934. PubMed DOI PMC

Boyle AP, Davis S, Shulha HP, Meltzer P, Margulies EH, Weng Z, Furey TS, Crawford GE. High-resolution mapping and characterization of open chromatin across the genome. Cell. 2008;132(2):311–322. doi: 10.1016/j.cell.2007.12.014. PubMed DOI PMC

Steijger T, Abril JF, Engstrom PG, Kokocinski F, Hubbard TJ, Guigo R, Harrow J, Bertone P, Consortium R. Assessment of transcript reconstruction methods for RNA-seq. Nat Methods. 2013;10(12):1177–1184. doi: 10.1038/nmeth.2714. PubMed DOI PMC

Serber Z, Lai HC, Yang A, Ou HD, Sigal MS, Kelly AE, Darimont BD, Duijf PH, Van Bokhoven H, McKeon F, et al. A C-terminal inhibitory domain controls the activity of p63 by an intramolecular mechanism. Mol Cell Biol. 2002;22(24):8601–8611. doi: 10.1128/MCB.22.24.8601-8611.2002. PubMed DOI PMC

Deutsch GB, Zielonka EM, Coutandin D, Weber TA, Schafer B, Hannewald J, Luh LM, Durst FG, Ibrahim M, Hoffmann J, et al. DNA damage in oocytes induces a switch of the quality control factor TAp63alpha from dimer to tetramer. Cell. 2011;144(4):566–576. doi: 10.1016/j.cell.2011.01.013. PubMed DOI PMC

Mangiulli M, Valletti A, Caratozzolo MF, Tullo A, Sbisa E, Pesole G, D’Erchia AM. Identification and functional characterization of two new transcriptional variants of the human p63 gene. Nucleic Acids Res. 2009;37(18):6092–6104. doi: 10.1093/nar/gkp674. PubMed DOI PMC

Gonzalez-Porta M, Frankish A, Rung J, Harrow J, Brazma A. Transcriptome analysis of human tissues and cell lines reveals one dominant transcript per gene. Genome Biol. 2013;14(7):R70. doi: 10.1186/gb-2013-14-7-r70. PubMed DOI PMC

Suzuki D, Sahu R, Leu NA, Senoo M. The carboxy-terminus of p63 links cell cycle control and the proliferative potential of epidermal progenitor cells. Development. 2015;142(2):282–290. doi: 10.1242/dev.118307. PubMed DOI PMC

Nekulova M, Holcakova J, Nenutil R, Stratmann R, Bouchalova P, Muller P, Moukova L, Coates PJ, Vojtesek B. Characterization of specific p63 and p63-N-terminal isoform antibodies and their application for immunohistochemistry. Virchows Arch. 2013;463(3):415–425. doi: 10.1007/s00428-013-1459-4. PubMed DOI

Dotsch V, Bernassola F, Coutandin D, Candi E, Melino G. p63 and p73, the ancestors of p53. Cold Spring Harb Perspect Biol. 2010;2(9):a004887. doi: 10.1101/cshperspect.a004887. PubMed DOI PMC

Pozniak CD, Barnabe-Heider F, Rymar VV, Lee AF, Sadikot AF, Miller FD. p73 is required for survival and maintenance of CNS neurons. J Neurosci. 2002;22(22):9800–9809. PubMed PMC

Talos F, Abraham A, Vaseva AV, Holembowski L, Tsirka SE, Scheel A, Bode D, Dobbelstein M, Bruck W, Moll UM. p73 is an essential regulator of neural stem cell maintenance in embryonal and adult CNS neurogenesis. Cell Death Differ. 2010;17(12):1816–1829. doi: 10.1038/cdd.2010.131. PubMed DOI PMC

Brosh R, Rotter V. When mutants gain new powers: news from the mutant p53 field. Nat Rev Cancer. 2009;9(10):701–713. PubMed

McDade SS, Henry AE, Pivato GP, Kozarewa I, Mitsopoulos C, Fenwick K, Assiotis I, Hakas J, Zvelebil M, Orr N, et al. Genome-wide analysis of p63 binding sites identifies AP-2 factors as co-regulators of epidermal differentiation. Nucleic Acids Res. 2012;40(15):7190–7206. doi: 10.1093/nar/gks389. PubMed DOI PMC

Radoja N, Guerrini L, Lo Iacono N, Merlo GR, Costanzo A, Weinberg WC, La Mantia G, Calabro V, Morasso MI. Homeobox gene Dlx3 is regulated by p63 during ectoderm development: relevance in the pathogenesis of ectodermal dysplasias. Development. 2007;134(1):13–18. doi: 10.1242/dev.02703. PubMed DOI

Vigano MA, Lamartine J, Testoni B, Merico D, Alotto D, Castagnoli C, Robert A, Candi E, Melino G, Gidrol X, et al. New p63 targets in keratinocytes identified by a genome-wide approach. Embo J. 2006;25(21):5105–5116. doi: 10.1038/sj.emboj.7601375. PubMed DOI PMC

Sethi I, Sinha S, Buck MJ. Role of chromatin and transcriptional co-regulators in mediating p63-genome interactions in keratinocytes. BMC Genomics. 2014;15:1042. doi: 10.1186/1471-2164-15-1042. PubMed DOI PMC

Tandon B, Peterson L, Gao J, Nelson B, Ma S, Rosen S, Chen YH. Nuclear overexpression of lymphoid-enhancer-binding factor 1 identifies chronic lymphocytic leukemia/small lymphocytic lymphoma in small B-cell lymphomas. Mod Pathol. 2011;24(11):1433–1443. doi: 10.1038/modpathol.2011.103. PubMed DOI

Tinguely M, Thies S, Frigerio S, Reineke T, Korol D, Zimmermann DR. IRF8 is associated with germinal center B-cell-like type of diffuse large B-cell lymphoma and exceptionally involved in translocation t(14;16)(q32.33;q24.1) Leuk Lymphoma. 2014;55(1):136–142. doi: 10.3109/10428194.2013.793324. PubMed DOI

Drewelus I, Gopfert C, Hippel C, Dickmanns A, Damianitsch K, Pieler T, Dobbelstein M. p63 antagonizes Wnt-induced transcription. Cell Cycle. 2010;9(3):580–587. doi: 10.4161/cc.9.3.10593. PubMed DOI

Kouwenhoven EN, van Heeringen SJ, Tena JJ, Oti M, Dutilh BE, Alonso ME, de la Calle-Mustienes E, Smeenk L, Rinne T, Parsaulian L, et al. Genome-wide profiling of p63 DNA-binding sites identifies an element that regulates gene expression during limb development in the 7q21 SHFM1 locus. PLoS Genet. 2010;6(8):e1001065. doi: 10.1371/journal.pgen.1001065. PubMed DOI PMC

Humphries LA, Godbersen JC, Danilova OV, Kaur P, Christensen BC, Danilov AV. Pro-apoptotic TP53 homolog TAp63 is repressed via epigenetic silencing and B-cell receptor signalling in chronic lymphocytic leukaemia. Br J Haematol. 2013;163(5):590–602. doi: 10.1111/bjh.12580. PubMed DOI PMC

Walther N, Ulrich A, Vockerodt M, von Bonin F, Klapper W, Meyer K, Eberth S, Pukrop T, Spang R, Trumper L, et al. Aberrant lymphocyte enhancer-binding factor 1 expression is characteristic for sporadic Burkitt’s lymphoma. Am J Pathol. 2013;182(4):1092–1098. doi: 10.1016/j.ajpath.2012.12.013. PubMed DOI

Satterwhite E, Sonoki T, Willis TG, Harder L, Nowak R, Arriola EL, Liu H, Price HP, Gesk S, Steinemann D, et al. The BCL11 gene family: involvement of BCL11A in lymphoid malignancies. Blood. 2001;98(12):3413–3420. doi: 10.1182/blood.V98.12.3413. PubMed DOI

Fagerberg L, Hallstrom BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, Habuka M, Tahmasebpoor S, Danielsson A, Edlund K, et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 2014;13(2):397–406. doi: 10.1074/mcp.M113.035600. PubMed DOI PMC

Forrest AR, Kawaji H, Rehli M, Baillie JK, de Hoon MJ, Haberle V, Lassman T, Kulakovskiy IV, Lizio M, Itoh M, et al. A promoter-level mammalian expression atlas. Nature. 2014;507(7493):462–470. doi: 10.1038/nature13182. PubMed DOI PMC

Brenner JC, Graham MP, Kumar B, Saunders LM, Kupfer R, Lyons RH, Bradford CR, Carey TE. Genotyping of 73 UM-SCC head and neck squamous cell carcinoma cell lines. Head Neck. 2010;32(4):417–426. PubMed PMC

Owen JH, Hauff SJ, Tang AL, Graham MP, Czerwinski MJ, Kaddoura M, Papagerakis S, Bradford CR, Carey TE, Prince ME. UM-SCC-103: a unique tongue cancer cell line that recapitulates the tumorigenic stem cell population of the primary tumor. Ann Otol Rhinol Laryngol. 2014;123(9):662–672. doi: 10.1177/0003489414531910. PubMed DOI PMC

Langmead B, Trapnell C, Pop M, Salzberg SL. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009;10(3):R25. doi: 10.1186/gb-2009-10-3-r25. PubMed DOI PMC

de Hoon MJ, Imoto S, Nolan J, Miyano S. Open source clustering software. Bioinformatics. 2004;20(9):1453–1454. doi: 10.1093/bioinformatics/bth078. PubMed DOI

Saldanha AJ. Java Treeview--extensible visualization of microarray data. Bioinformatics. 2004;20(17):3246–3248. doi: 10.1093/bioinformatics/bth349. PubMed DOI

Romano RA, Birkaya B, Sinha S. A functional enhancer of keratin14 is a direct transcriptional target of deltaNp63. J Invest Dermatol. 2007;127(5):1175–1186. doi: 10.1038/sj.jid.5700652. PubMed DOI

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...