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Title: Super enhancer-mediated upregulation of HJURP promotes growth and survival of t(4;14)-positive multiple myeloma
Authors: Jia, Yunlu
Zhou, Jianbiao
Tan, Tze King
Chung, Tae-Hoon
Chen, Yongxia
Chooi, Jing-Yuan
Sanda, Takaomi
Fullwood, Melissa Jane
Xiong, Sinan
Toh, Sabrina H. M.
Balan, Kalpnaa
Wong, Regina W. J.
Lim, Julia S. L.
Zhang, Enfan
Cai, Zhen
Shen, Peng
Chng, Wee Joo
Keywords: Science::Biological sciences
Issue Date: 2022
Source: Jia, Y., Zhou, J., Tan, T. K., Chung, T., Chen, Y., Chooi, J., Sanda, T., Fullwood, M. J., Xiong, S., Toh, S. H. M., Balan, K., Wong, R. W. J., Lim, J. S. L., Zhang, E., Cai, Z., Shen, P. & Chng, W. J. (2022). Super enhancer-mediated upregulation of HJURP promotes growth and survival of t(4;14)-positive multiple myeloma. Cancer Research, 82(3), 406-418.
Journal: Cancer Research 
Abstract: Multiple myeloma is an incurable malignancy with marked clinical and genetic heterogeneity. The cytogenetic abnormality t(4;14) (p16.3;q32.3) confers aggressive behavior in multiple myeloma. Recently, essential oncogenic drivers in a wide range of cancers have been shown to be controlled by super-enhancers (SE). We used chromatin immunoprecipitation sequencing of the active enhancer marker histone H3 lysine 27 acetylation (H3K27ac) to profile unique SEs in t(4;14)-translocated multiple myeloma. The histone chaperone HJURP was aberrantly overexpressed in t(4;14)-positive multiple myeloma due to transcriptional activation by a distal SE induced by the histone lysine methyltransferase NSD2. Silencing of HJURP with short hairpin RNA or CRISPR interference of SE function impaired cell viability and led to apoptosis. Conversely, HJURP overexpression promoted cell proliferation and abrogated apoptosis. Mechanistically, the NSD2/BRD4 complex positively coregulated HJURP transcription by binding the promoter and active elements of its SE. In summary, this study introduces SE profiling as an efficient approach to identify new targets and understand molecular pathogenesis in specific subtypes of cancer. Moreover, HJURP could be a valuable therapeutic target in patients with t(4;14)-positive myeloma. SIGNIFICANCE: A super-enhancer screen in t(4;14) multiple myeloma serves to identify genes that promote growth and survival of myeloma cells, which may be evaluated in future studies as therapeutic targets.
ISSN: 0008-5472
DOI: 10.1158/0008-5472.CAN-21-0921
Schools: School of Biological Sciences 
Organisations: Cancer Science Institute of Singapore, NUS
Centre for Translational Medicine
Rights: © 2021 The Authors; Published by the American Association for Cancer Research. This open access article is distributed under Creative Commons AttributionNonCommercial-NoDerivatives License 4.0 International (CC BY-NC-ND).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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