Chromatin profiling reveals relocalization of lysine-specific demethylase 1 by an oncogenic fusion protein

References

• Burningham Z, Hashibe M, Spector L, et al. The epidemiology of sarcoma. Clin Sarcoma Res. 2012;2:14.
   Google Scholar
• Delattre O, Zucman J, Plougastel B, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature. 1992;359:162–165.
   Google Scholar
• Turc-Carel C, Philip I, Berger MP, et al. Chromosome study of Ewing’s sarcoma (ES) cell lines. Consistency of a reciprocal translocation t(11;22)(q24;q12). Cancer Genet Cytogenet. 1984;12(1):1–19. .
   Google Scholar
• Turc-Carel C, Aurias A, Mugneret F, et al. Chromosomes in Ewing’s sarcoma. I. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12). Cancer Genet. Cytogenet. 1988;32:229–238. .
   Google Scholar
• Boulay G, Sandoval GJ, Riggi N, et al. Cancer-specific retargeting of BAF complexes by a prion-like domain. Cell. 2017;171:163–178.e19.
   Google Scholar
• May WA, Gishizky ML, Lessnick SL, et al. Ewing sarcoma 11;22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FLI1 for transformation. Proc Natl Acad Sci USA. 1993;90:5752–5756.
   Google Scholar
• May WA, Lessnick SL, Braun BS, et al. The Ewing’s sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1. Mol. Cell. Biol. 1993;13:7393–7398.
   Google Scholar
• Riggi N, Knoechel B, Gillespie S, et al. EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma. Cancer Cell. 2014;26:668–681.
   Google Scholar
• Sankar S, Bell R, Stephens B, et al. Mechanism and relevance of EWS/FLI-mediated transcriptional repression in Ewing sarcoma. Oncogene. 2013;32:5089–5100.
   Google Scholar
• Smith R, Owen LA, Trem DJ, et al. Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing’s sarcoma. Cancer Cell. 2006;9:405–416.
   Google Scholar
• Tomazou EM, Sheffield N, Schmidl C, et al. Epigenome mapping reveals distinct modes of gene regulation and widespread enhancer reprogramming by the oncogenic fusion protein EWS-FLI1. Cell Rep. 2015;10:1082–1095.
   Google Scholar
• Gangwal K, Close D, Enriquez CA, et al. Emergent properties of EWS/FLI regulation via GGAA microsatellites in Ewing’s sarcoma. Genes Cancer. 2010;1:177–187.
   Google Scholar
• Gangwal K, Sankar S, Hollenhorst PC, et al. Microsatellites as EWS/FLI response elements in Ewing’s sarcoma. Proc Natl Acad Sci. 2008;105:10149–10154.
   Google Scholar
• Guillon N, Tirode F, Boeva V, et al. The oncogenic EWS-FLI1 protein binds in vivo GGAA microsatellite sequences with potential transcriptional activation function. PLoS ONE. 2009;4:e4932.
   Google Scholar
• Kwon I, Kato M, Xiang S, et al. Phosphorylation-regulated binding of RNA polymerase II to fibrous polymers of low-complexity domains. Cell. 2013;155:1049–1060.
   Google Scholar
• Theisen ER, Miller KR, Showpnil IA, et al. Transcriptomic analysis functionally maps the intrinsically disordered domain of EWS/FLI and reveals novel transcriptional dependencies for oncogenesis. Genes Cancer. 2019;10:21–38.
   Google Scholar
• Sankar S, Theisen ER, Bearss J, et al. Reversible LSD1 inhibition interferes with global EWS/ETS transcriptional activity and impedes Ewing sarcoma tumor growth. Clin Cancer Res. 2014;20:4584–4597.
   Google Scholar
• Shi Y, Lan F, Matson C, et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell. 2004;119:941–953.
   Google Scholar
• Metzger E, Wissmann M, Yin N, et al. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature. 2005;437:436–439.
   Google Scholar
• Huang J, Sengupta R, Espejo AB, et al. p53 is regulated by the lysine demethylase LSD1. Nature. 2007;449:105–108.
   Google Scholar
• Wang J, Hevi S, Kurash JK, et al. The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nat. Genet. 2009;41:125–129.
   Google Scholar
• Yang M, Gocke CB, Luo X, et al. Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase. Mol Cell. 2006;23:377–387.
   Google Scholar
• Whyte WA, Bilodeau S, Orlando DA, et al. Enhancer decommissioning by LSD1 during embryonic stem cell differentiation. Nature. 2012;482:221–225.
   Google Scholar
• Hatzi K, Geng H, Doane AS, et al. Histone demethylase LSD1 is required for germinal center formation and BCL6-driven lymphomagenesis. Nat. Immunol. 2019;20:86.
   Google Scholar
• Maiques-Diaz A, Spencer GJ, Lynch JT, et al. Enhancer activation by pharmacologic displacement of LSD1 from GFI1 induces differentiation in acute myeloid leukemia. Cell Rep. 2018;22:3641–3659.
   Google Scholar
• Sugino N, Kawahara M, Tatsumi G, et al. A novel LSD1 inhibitor NCD38 ameliorates MDS-related leukemia with complex karyotype by attenuating leukemia programs via activating super-enhancers. Leukemia. 2017;31:2303–2314.
   Google Scholar
• Harris WJ, Huang X, Lynch J, et al. The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells. Cancer Cell. 2012;21:473–487.
   Google Scholar
• Hayami S, Kelly JD, Cho H-S, et al. Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. Int J Cancer. 2011;128:574–586.
   Google Scholar
• Kahl P, Gullotti L, Heukamp LC, et al. Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence. Cancer Res. 2006;66:11341–11347.
   Google Scholar
• Lim S, Janzer A, Becker A, et al. Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology. Carcinogenesis. 2010;31:512–520.
   Google Scholar
• Schulte JH, Lim S, Schramm A, et al. Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy. Cancer Res. 2009;69:2065–2071.
   Google Scholar
• Bennani-Baiti IM, Machado I, Llombart-Bosch A, et al. Lysine-specific demethylase 1 (LSD1/KDM1A/AOF2/BHC110) is expressed and is an epigenetic drug target in chondrosarcoma, Ewing’s sarcoma, osteosarcoma, and rhabdomyosarcoma. Hum Pathol. 2012;43:1300–1307.
   Google Scholar
• Schildhaus H-U, Riegel R, Hartmann W, et al. Lysine-specific demethylase 1 is highly expressed in solitary fibrous tumors, synovial sarcomas, rhabdomyosarcomas, desmoplastic small round cell tumors, and malignant peripheral nerve sheath tumors. Hum. Pathol. 2011;42:1667–1675.
   Google Scholar
• Pishas KI, Drenberg CD, Taslim C, et al. Therapeutic targeting of KDM1A/LSD1 in Ewing sarcoma with SP-2509 engages the endoplasmic reticulum stress response. Mol Cancer Ther. 2018;17:1902–1916.
   Google Scholar
• Zhao Z-K, Yu HF, Wang DR, et al. Overexpression of lysine specific demethylase 1 predicts worse prognosis in primary hepatocellular carcinoma patients. World J Gastroenterol. 2012;18:6651–6656.
   Google Scholar
• Sankar S, Gomez NC, Bell R, et al. EWS and RE1-silencing transcription factor inhibit neuronal phenotype development and oncogenic transformation in Ewing sarcoma. Genes Cancer. 2013;4:213–223.
   Google Scholar
• Skene PJ, Henikoff S. An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites. eLife. 2017;6:e21856.
   Google Scholar
• Melot T, GRUEL N, DOUBEIKOVSKI A, et al. Production and characterization of mouse monoclonal antibodies to wild-type and oncogenic FLI-1 proteins. Hybridoma. 1997;16:457–464.
   Google Scholar
• Johnson KM, Taslim C, Saund RS, et al. Identification of two types of GGAA-microsatellites and their roles in EWS/FLI binding and gene regulation in Ewing sarcoma. Plos One. 2017;12:e0186275.
   Google Scholar
• Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci. 2005;102:15545–15550.
   Google Scholar
• Boulay G, Volorio A, Iyer S, et al. Epigenome editing of microsatellite repeats defines tumor-specific enhancer functions and dependencies. Genes Dev. 2018. DOI:10.1101/gad.315192.118.
   Google Scholar
• Lovén J, Hoke H, Lin C, et al. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell. 2013;153:320–334.
   Google Scholar
• Whyte WA, Orlando D, Hnisz D, et al. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell. 2013;153:307–319.
   Google Scholar
• Kennedy AL, Vallurupalli M, Chen L, et al. Functional, chemical genomic, and super-enhancer screening identify sensitivity to cyclin D1/CDK4 pathway inhibition in Ewing sarcoma. Oncotarget. 2015;6:30178–30193.
   Google Scholar
• Johnson KM, Mahler NR, Saund RS, et al. Role for the EWS domain of EWS/FLI in binding GGAA-microsatellites required for Ewing sarcoma anchorage independent growth. Proc Natl Acad Sci USA. 2017;114:9870–9875.
   Google Scholar
• Hnisz D, Abraham B, Lee T, et al. Super-enhancers in the control of cell identity and disease. Cell. 2013;155(4):934–947. .
   Google Scholar
• Agarwal S, Garay PM, Porter RS, et al. LSD1/KDM1A maintains genome-wide homeostasis of transcriptional enhancers. bioRxiv. 2017;146357. DOI:10.1101/146357.
   Google Scholar
• Kearns NA, Pham H, Tabak B, et al. Functional annotation of native enhancers with a Cas9-histone demethylase fusion. Nat Methods. 2015;12:401–403.
   Google Scholar
• Mendenhall EM, Williamson KE, Reyon D, et al. Locus-specific editing of histone modifications at endogenous enhancers. Nat Biotechnol. 2013;31:1133–1136.
   Google Scholar
• Lee C, Rudneva VA, Erkek S, et al. Lsd1 as a therapeutic target in Gfi1-activated medulloblastoma. Nat Commun. 2019;10:332.
   Google Scholar
• Cai C, He H, Gao S, et al. Lysine-specific demethylase 1 has dual functions as a major regulator of androgen receptor transcriptional activity. Cell Rep. 2014;9:1618–1627.
   Google Scholar
• Sehrawat A, Gao L, Wang Y, et al. LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci USA. 2018;115:E4179–E4188.
   Google Scholar
• Kaya-Okur HS, Wu SJ, Codomo CA, et al. CUT&Tag for efficient epigenomic profiling of small samples and single cells. Nat Commun. 2019;10:1–10.
   Google Scholar
• Buenrostro JD, Wu B, Litzenburger UM, et al. Single-cell chromatin accessibility reveals principles of regulatory variation. Nature. 2015;523:486–490.
   Google Scholar
• Andrews S FastQC: a quality control tool for high throughput sequence data.
   Google Scholar
• Krueger F. Trim galore!: A wrapper tool around cutadapt and FastQC to consistently apply quality and adapter trimming to FastQ files. Cambridge (UK): Babraham Institute; 2015.
   Google Scholar
• Tools (written in C using htslib) for manipulating next-generation sequencing data: samtools/samtools. samtools. 2019.
   Google Scholar
• Dale RK, Pedersen BS, Quinlan AR. Pybedtools: a flexible python library for manipulating genomic datasets and annotations. Bioinformatics. 2011;27:3423–3424.
   Google Scholar
• Feng J, Liu T, Qin B, et al. Identifying ChIP-seq enrichment using MACS. Nat Protoc. 2012;7. DOI:10.1038/nprot.2012.101
   Google Scholar
• Lun ATL, Smyth GK. csaw: a bioconductor package for differential binding analysis of ChIP-seq data using sliding windows. Nucleic Acids Res. 2016;44:e45.
   Google Scholar
• Zhu LJ, Gazin C, Lawson ND, et al. ChIPpeakAnno: a bioconductor package to annotate ChIP-seq and ChIP-chip data. BMC Bioinformatics. 2010;11:237.
   Google Scholar
• Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010;26:841–842.
   Google Scholar
• Heinz S, Benner C, Spann N, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38:576–589.
   Google Scholar
• Mootha VK,Lindgren CM, Eriksson KF, et al. PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34:267.
   Google Scholar
• Ramírez F, Ryan DP, Grüning B, et al. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 2016;44:W160–W165.
   Google Scholar