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Research: Epigenomic translocation of H3K4me3 broad domains over oncogenes following hijacking of super-enhancers
- Aneta Mikulasova,
- Daniel Kent,
- Marco Trevisan-Herraz,
- Nefeli Karataraki,
- Kent T.M. Fung,
- Cody Ashby,
- Agata Cieslak,
- Shmuel Yaccoby,
- Frits van Rhee,
- Maurizio Zangari,
- Sharmilan Thanendrarajan,
- Carolina Schinke,
- Gareth J. Morgan,
- Vahid Asnafi,
- Salvatore Spicuglia,
- Chris A. Brackley,
- Anne E. Corcoran,
- Sophie Hambleton,
- Brian A. Walker,
- Daniel Rico,
- and Lisa J. Russell
Genome Res. July 2022 32: 1343-1354; Published in Advance December 21, 2021, doi:10.1101/gr.276042.121
...of H3K4me3-BD over CCND1 in the latter was associated with overexpression and extensive chromatin accessibility of its gene body. We observed similar cancer-specific H3K4me3-BDs associated with hijacking of super-enhancers of other common oncogenes in B cell (MAF, MYC, and FGFR3/NSD2) and T cell...
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Research: Chromatin interaction maps identify oncogenic targets of enhancer duplications in cancer
- Yueqiang Song,
- Fuyuan Li,
- Shangzi Wang,
- Yuntong Wang,
- Cong Lai,
- Lian Chen,
- Ning Jiang,
- Jin Li,
- Xingdong Chen,
- Swneke D. Bailey,
- and Xiaoyang Zhang
Genome Res. October 2024 34: 1514-1527; Published in Advance October 18, 2024, doi:10.1101/gr.278418.123
...subjects of duplications in cancer. For instance, distal enhancers of oncogenes such as KLF5, AR, SOX2, MYC, and EGFR are selectively duplicated with or without the oncogenes in diverse cancer types, which activates their expression through up to 800 kb long-distance enhancer–promoter interactions (Zhang...
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Research: Active enhancers strengthen insulation by RNA-mediated CTCF binding at chromatin domain boundaries
- Zubairul Islam,
- Bharath Saravanan,
- Kaivalya Walavalkar,
- Umer Farooq,
- Anurag Kumar Singh,
- Sabarinathan Radhakrishnan,
- Jitendra Thakur,
- Awadhesh Pandit,
- Steven Henikoff,
- and Dimple Notani
Genome Res. January 2023 33: 1-17; Published in Advance January 17, 2023, doi:10.1101/gr.276643.122
.... The green looping tracks show the gain of interactions upon global CTCF knockdown. (D) qRT-PCRs showing the levels of sense and antisense RNA from MYC gene upon their shRNA-mediated knockdowns in a chromatin-associated RNA fraction. The level of RNA at Chr 11 boundary does not change. (E) CTCF Ch...
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Resource: A temporal in vivo catalog of chromatin accessibility and expression profiles in pineoblastoma reveals a prevalent role for repressor elements
- Salam Idriss,
- Mohammad Hallal,
- Abdullah El-Kurdi,
- Hasan Zalzali,
- Inaam El-Rassi,
- Erik A. Ehli,
- Christel M. Davis,
- Philip E.D. Chung,
- Deena M.A. Gendoo,
- Eldad Zacksenhaus,
- Raya Saab,
- and Pierre Khoueiry
Genome Res. February 2023 33: 269-282; Published in Advance January 17, 2023, doi:10.1101/gr.277037.122
...mutations in DICER1 and RB1 genes are known predisposing factors (de Kock et al. 2014, 2020), but also sporadic PB events are frequent with a major role for MYC amplification (Li et al. 2020; Liu et al. 2021). Moreover, DNA methylation profiling and whole-exome sequencing revealed a homozygous deletion...
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Method: High-resolution simulations of chromatin folding at genomic rearrangements in malignant B cells provide mechanistic insights into proto-oncogene deregulation
- Daniel Rico,
- Daniel Kent,
- Nefeli Karataraki,
- Aneta Mikulasova,
- Rolando Berlinguer-Palmini,
- Brian A. Walker,
- Biola M. Javierre,
- Lisa J. Russell,
- and Chris A. Brackley
Genome Res. July 2022 32: 1355-1366; Published in Advance July 21, 2022, doi:10.1101/gr.276028.121
...also observed extensive changes in enhancer-promoter interactions within the TAD, suggesting that it is the downstream chromatin remodeling which gives rise to the oncogene activation, rather than the presence of the inserted super-enhancer DNA sequence per se. Simulations of the IGH-CCND1 reciprocal...
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Research: Chromatin activation as a unifying principle underlying pathogenic mechanisms in multiple myeloma
- Raquel Ordoñez,
- Marta Kulis,
- Nuria Russiñol,
- Vicente Chapaprieta,
- Arantxa Carrasco-Leon,
- Beatriz García-Torre,
- Stella Charalampopoulou,
- Guillem Clot,
- Renée Beekman,
- Cem Meydan,
- Martí Duran-Ferrer,
- Núria Verdaguer-Dot,
- Roser Vilarrasa-Blasi,
- Paula Soler-Vila,
- Leire Garate,
- Estíbaliz Miranda,
- Edurne San José-Enériz,
- Juan R. Rodriguez-Madoz,
- Teresa Ezponda,
- Rebeca Martínez-Turrilas,
- Amaia Vilas-Zornoza,
- David Lara-Astiaso,
- Daphné Dupéré-Richer,
- Joost H.A. Martens,
- Halima El-Omri,
- Ruba Y. Taha,
- Maria J. Calasanz,
- Bruno Paiva,
- Jesus San Miguel,
- Paul Flicek,
- Ivo Gut,
- Ari Melnick,
- Constantine S. Mitsiades,
- Jonathan D. Licht,
- Elias Campo,
- Hendrik G. Stunnenberg,
- Xabier Agirre,
- Felipe Prosper,
- and Jose I. Martin-Subero
Genome Res. September 2020 30: 1217-1227; Published in Advance August 20, 2020, doi:10.1101/gr.265520.120
...that this transcription factor regulates a complex transcriptional regulatory network, implicated in multiple cellular processes and signaling pathways (such as TNF, IL2-STAT5, KRAS, MTOR, MYC, or TP53). Out of these, we detected that genes down-regulated upon PRDM5 silencing were associated with the cell cycle as well...
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Research: A KMT2A-AFF1 gene regulatory network highlights the role of core transcription factors and reveals the regulatory logic of key downstream target genes
- Joe R. Harman,
- Ross Thorne,
- Max Jamilly,
- Marta Tapia,
- Nicholas T. Crump,
- Siobhan Rice,
- Ryan Beveridge,
- Edward Morrissey,
- Marella F.T.R. de Bruijn,
- Irene Roberts,
- Anindita Roy,
- Tudor A. Fulga,
- and Thomas A. Milne
Genome Res. July 2021 31: 1159-1173; Published in Advance June 4, 2021, doi:10.1101/gr.268490.120
...leukemias (AMLs). KMT2A-AFF1 drives leukemogenesis through direct binding and inducing the aberrant overexpression of key genes, such as the anti-apoptotic factor BCL2 and the proto-oncogene MYC. However, studying direct binding alone does not incorporate possible network-generated regulatory outputs...
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Research: Diverse tumorigenic consequences of human papillomavirus integration in primary oropharyngeal cancers
- David E. Symer,
- Keiko Akagi,
- Heather M. Geiger,
- Yang Song,
- Gaiyun Li,
- Anne-Katrin Emde,
- Weihong Xiao,
- Bo Jiang,
- André Corvelo,
- Nora C. Toussaint,
- Jingfeng Li,
- Amit Agrawal,
- Enver Ozer,
- Adel K. El-Naggar,
- Zoe Du,
- Jitesh B. Shewale,
- Birgit Stache-Crain,
- Mark Zucker,
- Nicolas Robine,
- Kevin R. Coombes,
- and Maura L. Gillison
Genome Res. January 2022 32: 55-70; Published in Advance December 13, 2021, doi:10.1101/gr.275911.121
...upstream of MYC. Both are associated with elevated MYC transcript levels (Fig. 2C; Supplemental Figs. S2.1, S2.2), consistent with impacts of amplification of the gene or adjacent super-enhancers (Zhang et al. 2016). HPV integration near MYC previously was reported in cervical cancers and derived cell...
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Research: Alu insertion variants alter gene transcript levels
- Lindsay M. Payer,
- Jared P. Steranka,
- Maria S. Kryatova,
- Giacomo Grillo,
- Mathieu Lupien,
- Pedro P. Rocha,
- and Kathleen H. Burns
Genome Res. December 2021 31: 2236-2248; Published in Advance November 19, 2021, doi:10.1101/gr.261305.120
...in the reporter assay. We used CRISPR to modify the endogenous sequences, establishing cell lines varying in the Alu genotype. Our findings indicate that Alu genotype can alter expression of genes implicated in cancer risk, including PTHLH, RANBP9, and MYC. These data show that commonly occurring polymorphic Alu...
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Research: Histone deacetylases maintain expression of the pluripotent gene network via recruitment of RNA polymerase II to coding and noncoding loci
- Richard D.W. Kelly,
- Kristy R. Stengel,
- Aditya Chandru,
- Lyndsey C. Johnson,
- Scott W. Hiebert,
- and Shaun M. Cowley
Genome Res. January 2024 34: 34-46; Published in Advance January 30, 2024, doi:10.1101/gr.278050.123
...bodies, suggesting an alternative and nonrepressive function (Wang et al. 2009; Kidder and Palmer 2012; Whyte et al. 2012). In tumor cells, HDAC inhibition reduced the activity of superenhancers (SEs) via aberrant hyperacetylation, causing down-regulation of SE-driven transcription of genes such as Myc...
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