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Super-enhancers: critical roles and therapeutic targets in hematologic malignancies

Super-enhancers (SEs) in a broad range of human cell types are large clusters of enhancers with aberrant high levels of transcription factor binding, which are central to drive expression of genes in controlling cell identity and stimulating oncogenic transcription. Cancer cells acquire super-enhanc...

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Detalles Bibliográficos
Autores principales: Jia, Yunlu, Chng, Wee-Joo, Zhou, Jianbiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636097/
https://www.ncbi.nlm.nih.gov/pubmed/31311566
http://dx.doi.org/10.1186/s13045-019-0757-y
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author Jia, Yunlu
Chng, Wee-Joo
Zhou, Jianbiao
author_facet Jia, Yunlu
Chng, Wee-Joo
Zhou, Jianbiao
author_sort Jia, Yunlu
collection PubMed
description Super-enhancers (SEs) in a broad range of human cell types are large clusters of enhancers with aberrant high levels of transcription factor binding, which are central to drive expression of genes in controlling cell identity and stimulating oncogenic transcription. Cancer cells acquire super-enhancers at oncogene and cancerous phenotype relies on these abnormal transcription propelled by SEs. Furthermore, specific inhibitors targeting SEs assembly and activation have offered potential targets for treating various tumors including hematological malignancies. Here, we first review the identification, functional significance of SEs. Next, we summarize recent findings of SEs and SE-driven gene regulation in normal hematopoiesis and hematologic malignancies. The importance and various modes of SE-mediated MYC oncogene amplification are illustrated. Finally, we highlight the progress of SEs as selective therapeutic targets in basic research and clinical trials. Some open questions regarding functional significance and future directions of targeting SEs in the clinic will be discussed too.
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spelling pubmed-66360972019-07-25 Super-enhancers: critical roles and therapeutic targets in hematologic malignancies Jia, Yunlu Chng, Wee-Joo Zhou, Jianbiao J Hematol Oncol Review Super-enhancers (SEs) in a broad range of human cell types are large clusters of enhancers with aberrant high levels of transcription factor binding, which are central to drive expression of genes in controlling cell identity and stimulating oncogenic transcription. Cancer cells acquire super-enhancers at oncogene and cancerous phenotype relies on these abnormal transcription propelled by SEs. Furthermore, specific inhibitors targeting SEs assembly and activation have offered potential targets for treating various tumors including hematological malignancies. Here, we first review the identification, functional significance of SEs. Next, we summarize recent findings of SEs and SE-driven gene regulation in normal hematopoiesis and hematologic malignancies. The importance and various modes of SE-mediated MYC oncogene amplification are illustrated. Finally, we highlight the progress of SEs as selective therapeutic targets in basic research and clinical trials. Some open questions regarding functional significance and future directions of targeting SEs in the clinic will be discussed too. BioMed Central 2019-07-16 /pmc/articles/PMC6636097/ /pubmed/31311566 http://dx.doi.org/10.1186/s13045-019-0757-y Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Review
Jia, Yunlu
Chng, Wee-Joo
Zhou, Jianbiao
Super-enhancers: critical roles and therapeutic targets in hematologic malignancies
title Super-enhancers: critical roles and therapeutic targets in hematologic malignancies
title_full Super-enhancers: critical roles and therapeutic targets in hematologic malignancies
title_fullStr Super-enhancers: critical roles and therapeutic targets in hematologic malignancies
title_full_unstemmed Super-enhancers: critical roles and therapeutic targets in hematologic malignancies
title_short Super-enhancers: critical roles and therapeutic targets in hematologic malignancies
title_sort super-enhancers: critical roles and therapeutic targets in hematologic malignancies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636097/
https://www.ncbi.nlm.nih.gov/pubmed/31311566
http://dx.doi.org/10.1186/s13045-019-0757-y
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