title: Deep sequencing of MYC DNA-binding sites in Burkitt lymphoma.
abstract: BACKGROUND
  MYC is a key transcription factor involved in central cellular processes such as regulation of the cell cycle, histone acetylation and ribosomal biogenesis. It is overexpressed in the majority of human tumors including aggressive B-cell lymphoma. Especially Burkitt lymphoma (BL) is a highlight example for MYC overexpression due to a chromosomal translocation involving the c-MYC gene. However, no genome-wide analysis of MYC-binding sites by chromatin immunoprecipitation (ChIP) followed by next generation sequencing (ChIP-Seq) has been conducted in BL so far.
  
  
  RESULTS
  ChIP-Seq was performed on 5 BL cell lines with a MYC-specific antibody giving rise to 7,054 MYC-binding sites after bioinformatics analysis of a total of approx. 19 million sequence reads. In line with previous findings, binding sites accumulate in gene sets known to be involved in the cell cycle, ribosomal biogenesis, histone acetyltransferase and methyltransferase complexes demonstrating a regulatory role of MYC in these processes. Unexpectedly, MYC-binding sites also accumulate in many B-cell relevant genes. To assess the functional consequences of MYC binding, the ChIP-Seq data were supplemented with siRNA- mediated knock-downs of MYC in BL cell lines followed by gene expression profiling. Interestingly, amongst others, genes involved in the B-cell function were up-regulated in response to MYC silencing.
  
  
  CONCLUSIONS
  The 7,054 MYC-binding sites identified by our ChIP-Seq approach greatly extend the knowledge regarding MYC binding in BL and shed further light on the enormous complexity of the MYC regulatory network. Especially our observations that (i) many B-cell relevant genes are targeted by MYC and (ii) that MYC down-regulation leads to an up-regulation of B-cell genes highlight an interesting aspect of BL biology.
authors.affiliation: Institute of Pathology, Charité-University Medicine, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Volkhard
authors.initials: V
authors.lastname: Seitz
authors.forename: Peter
authors.initials: P
authors.lastname: Butzhammer
authors.forename: Burkhard
authors.initials: B
authors.lastname: Hirsch
authors.forename: Jochen
authors.initials: J
authors.lastname: Hecht
authors.forename: Ines
authors.initials: I
authors.lastname: Gütgemann
authors.forename: Anke
authors.initials: A
authors.lastname: Ehlers
authors.forename: Dido
authors.initials: D
authors.lastname: Lenze
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Oker
authors.forename: Anke
authors.initials: A
authors.lastname: Sommerfeld
authors.forename: Edda
authors.initials: E
authors.lastname: von der Wall
authors.forename: Christoph
authors.initials: C
authors.lastname: König
authors.forename: Christian
authors.initials: C
authors.lastname: Zinser
authors.forename: Rainer
authors.initials: R
authors.lastname: Spang
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
mesh_terms: D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000235:genetics; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004273:DNA, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering
references.citation: Genes Cancer. 2010 Jun 1;1(6):568-575
references.pmid: 20882107
references.citation: Cancer Res. 2007 Jun 1;67(11):5061-3
references.pmid: 17545579
references.citation: Genome Biol. 2009;10(3):R25
references.pmid: 19261174
references.citation: Nat Protoc. 2009;4(1):44-57
references.pmid: 19131956
references.citation: Cell Stem Cell. 2010 Sep 3;7(3):299-313
references.pmid: 20804967
references.citation: Genome Biol. 2003;4(10):R69
references.pmid: 14519204
references.citation: Genome Biol. 2003;4(5):P3
references.pmid: 12734009
references.citation: J Immunol. 2011 Jun 15;186(12):6726-36
references.pmid: 21572027
references.citation: Semin Cancer Biol. 2006 Aug;16(4):253-64
references.pmid: 16904903
references.citation: BMC Bioinformatics. 2010 May 11;11:237
references.pmid: 20459804
references.citation: Nat Genet. 2008 Jan;40(1):43-50
references.pmid: 18066065
references.citation: Genes Dev. 1999 Oct 15;13(20):2678-90
references.pmid: 10541554
references.citation: J Cell Biochem. 2008 Oct 15;105(3):670-7
references.pmid: 18773413
references.citation: J Biol Chem. 2003 May 30;278(22):20405-12
references.pmid: 12660246
references.citation: BMC Genomics. 2008 Sep 24;9:442
references.pmid: 18816399
references.citation: Bioinformatics. 2002;18 Suppl 1:S96-104
references.pmid: 12169536
references.citation: EMBO Rep. 2003 May;4(5):484-90
references.pmid: 12776737
references.citation: Oncogene. 2001 Sep 10;20(40):5595-610
references.pmid: 11607812
references.citation: PLoS One. 2010 Mar 15;5(3):e9691
references.pmid: 20300622
references.citation: J Biol Chem. 2001 Dec 21;276(51):48562-71
references.pmid: 11673469
references.citation: Leuk Lymphoma. 2002 Jan;43(1):159-64
references.pmid: 11908722
references.citation: Leukemia. 2011 Dec;25(12):1869-1876
references.pmid: 21701491
references.citation: Oncogene. 1993 Nov;8(11):3161-4
references.pmid: 8414519
references.citation: J Oncol. 2010;2010:
references.pmid: 20953370
references.citation: Comput Appl Biosci. 1996 Feb;12(1):71-80
references.pmid: 8670622
references.citation: Behav Brain Res. 2001 Nov 1;125(1-2):279-84
references.pmid: 11682119
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8164-9
references.pmid: 12808131
references.citation: J Clin Oncol. 2000 Nov 1;18(21):3707-21
references.pmid: 11054444
references.citation: Nat Rev Mol Cell Biol. 2006 Aug;7(8):557-67
references.pmid: 16936696
references.citation: Genome Biol. 2010;11(10):R106
references.pmid: 20979621
references.citation: Nature. 2005 Jun 9;435(7043):839-43
references.pmid: 15944709
references.citation: Leuk Lymphoma. 1998 Jul;30(3-4):257-67
references.pmid: 9713958
references.citation: Curr Top Microbiol Immunol. 2006;302:63-122
references.pmid: 16620026
references.citation: Nat Cell Biol. 2010 Mar;12(3):247-56
references.pmid: 20173740
references.citation: Mutat Res. 2008 Dec 1;647(1-2):3-12
references.pmid: 18682256
references.citation: Biotechniques. 2008 Aug;45(2):131-2, 134, 136 passim
references.pmid: 18687062
references.citation: Mol Cell. 2010 May 28;38(4):576-89
references.pmid: 20513432
references.citation: Blood. 2005 Aug 1;106(3):1031-6
references.pmid: 15840698
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17834-9
references.pmid: 17093053
references.citation: Nucl Recept Signal. 2003;1:e012
references.pmid: 16604184
references.citation: Am J Pathol. 2008 Feb;172(2):510-20
references.pmid: 18187570
references.citation: EMBO Rep. 2003 Jun;4(6):575-80
references.pmid: 12776177
references.citation: Adv Cancer Res. 2002;84:81-154
references.pmid: 11885563
references.citation: Nat Protoc. 2006;1(2):729-48
references.pmid: 17406303
references.citation: EMBO J. 2005 Jan 26;24(2):336-46
references.pmid: 15616584
references.citation: Mol Cell. 1999 Aug;4(2):199-207
references.pmid: 10488335
references.citation: Br J Haematol. 2010 May;149(4):484-97
references.pmid: 20346013
references.citation: Nat Rev Genet. 2010 Jul;11(7):476-86
references.pmid: 20531367
references.citation: PLoS One. 2008 Jul 16;3(7):e2722
references.pmid: 18628958
references.citation: Semin Cancer Biol. 2006 Aug;16(4):242-52
references.pmid: 16935524
references.citation: Exp Cell Res. 2003 Feb 1;283(1):17-21
references.pmid: 12565816