Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41408-021-00421-7
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dc.titleMyeloma-specific superenhancers affect genes of biological and clinical relevance in myeloma
dc.contributor.authorJia, Yunlu
dc.contributor.authorZhou, Jianbiao
dc.contributor.authorTan, Tze King
dc.contributor.authorChung, Tae-Hoon
dc.contributor.authorWong, Regina Wan Ju
dc.contributor.authorChooi, Jing-Yuan
dc.contributor.authorLim, Julia Sze Lynn
dc.contributor.authorSanda, Takaomi
dc.contributor.authorOoi, Melissa
dc.contributor.authorDe Mel, Sanjay
dc.contributor.authorSoekojo, Cinnie
dc.contributor.authorChen, Yongxia
dc.contributor.authorZhang, Enfan
dc.contributor.authorCai, Zhen
dc.contributor.authorShen, Peng
dc.contributor.authorRuan, Jian
dc.contributor.authorChng, Wee-Joo
dc.date.accessioned2021-11-11T06:44:51Z
dc.date.available2021-11-11T06:44:51Z
dc.date.issued2021-02-12
dc.identifier.citationJia, Yunlu, Zhou, Jianbiao, Tan, Tze King, Chung, Tae-Hoon, Wong, Regina Wan Ju, Chooi, Jing-Yuan, Lim, Julia Sze Lynn, Sanda, Takaomi, Ooi, Melissa, De Mel, Sanjay, Soekojo, Cinnie, Chen, Yongxia, Zhang, Enfan, Cai, Zhen, Shen, Peng, Ruan, Jian, Chng, Wee-Joo (2021-02-12). Myeloma-specific superenhancers affect genes of biological and clinical relevance in myeloma. BLOOD CANCER JOURNAL 11 (2). ScholarBank@NUS Repository. https://doi.org/10.1038/s41408-021-00421-7
dc.identifier.issn20445385
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/205901
dc.description.abstractMultiple myeloma (MM) is an aggressive plasma cell neoplasm characterized by genomic heterogeneity. Superenhancers (SEs) are defined as large clusters of enhancers in close genomic proximity, which regulate genes for maintaining cellular identity and promote oncogenic transcription to which cancer cells highly addicted. Here, we analyzed cis-regulatory elements in MM samples with H3K27ac ChIP-seq, to identify novel SE-associated genes involved in the myeloma pathogenesis. SEs and their associated genes in cancerous tissue were compared with the control samples, and we found SE analysis alone uncovered cell-lineage-specific transcription factors and well-known oncogenes ST3GAL6 and ADM. Using a transcriptional CDK7 inhibitor, THZ1, coupled with H3K27ac ChlP-seq, we identified MAGI2 as a novel SE-associated gene of myeloma cells. Elevated MAGI2 was related to myelomagenesis with gradual increased expression from MGUS, SMM to newly diagnosed and relapsed MM. High prevalence of MAGI2 was also associated with poor survival of MM patients. Importantly, inhibition of the SE activity associated with MAGI2 decreased MAGI2 expression, inhibited cell growth and induced cell apoptosis. Mechanistically, we revealed that the oncogenic transcription factor, MAF, directly bound to the SE region and activated gene transcription. In summary, the discoveries of these acquired SEs-associated genes and the novel mechanism by which they are regulated provide new insights into MM biology and MAGI2-MAF-SE regulatory circuit offer potential novel targets for disease treatment.
dc.language.isoen
dc.publisherSPRINGER NATURE
dc.sourceElements
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectOncology
dc.subjectHematology
dc.typeArticle
dc.date.updated2021-11-10T03:53:56Z
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEAN'S OFFICE (MEDICINE)
dc.contributor.departmentMEDICINE
dc.description.doi10.1038/s41408-021-00421-7
dc.description.sourcetitleBLOOD CANCER JOURNAL
dc.description.volume11
dc.description.issue2
dc.published.statePublished
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