Super-enhancers, phase-separated condensates, and 3D genome organization in cancer

3D chromatin organization plays an important role in transcription regulation and gene expression. The 3D genome is highly maintained by several architectural proteins, such as CTCF, Yin Yang 1, and cohesin complex. This structural organization brings regulatory DNA elements in close proximity to th...

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Main Authors: Tang, Seng Chuan, Vijayakumar, Udhaya, Zhang, Ying, Fullwood, Melissa Jane
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/169607
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1696072023-07-31T15:32:27Z Super-enhancers, phase-separated condensates, and 3D genome organization in cancer Tang, Seng Chuan Vijayakumar, Udhaya Zhang, Ying Fullwood, Melissa Jane School of Biological Sciences National University of Singapore Institute of Molecular and Cell Biology, A*STAR Science::Medicine Super-Enhancers Chromatin Looping 3D chromatin organization plays an important role in transcription regulation and gene expression. The 3D genome is highly maintained by several architectural proteins, such as CTCF, Yin Yang 1, and cohesin complex. This structural organization brings regulatory DNA elements in close proximity to their target promoters. In this review, we discuss the 3D chromatin organization of super-enhancers and their relationship to phase-separated condensates. Super-enhancers are large clusters of DNA elements. They can physically contact with their target promoters by chromatin looping during transcription. Multiple transcription factors can bind to enhancer and promoter sequences and recruit a complex array of transcriptional co-activators and RNA polymerase II to effect transcriptional activation. Phase-separated condensates of transcription factors and transcriptional co-activators have been implicated in assembling the transcription machinery at particular enhancers. Cancer cells can hijack super-enhancers to drive oncogenic transcription to promote cell survival and proliferation. These dysregulated transcriptional programs can cause cancer cells to become highly dependent on transcriptional regulators, such as Mediator and BRD4. Moreover, the expression of oncogenes that are driven by super-enhancers is sensitive to transcriptional perturbation and often occurs in phase-separated condensates, supporting therapeutic rationales of targeting SE components, 3D genome organization, or dysregulated condensates in cancer. Ministry of Education (MOE) National Research Foundation (NRF) Published version This research is supported by the RNA Biology Center at the Cancer Science Institute of Singapore, NUS, as part of funding under the Singapore Ministry of Education Academic Research Fund Tier 3 grant awarded to Daniel Tenen (MOE2014-T3-1-006). This research is supported by the NRF Singapore, and the Singapore Ministry of Education under its Research Centres of Excellence initiative and a Singapore Ministry of Education Academic Research Fund Tier 2 grant awarded to M.J.F. (MOE-T2EP30120-0009). 2023-07-26T01:38:22Z 2023-07-26T01:38:22Z 2022 Journal Article Tang, S. C., Vijayakumar, U., Zhang, Y. & Fullwood, M. J. (2022). Super-enhancers, phase-separated condensates, and 3D genome organization in cancer. Cancers, 14(12), 2866-. https://dx.doi.org/10.3390/cancers14122866 2072-6694 https://hdl.handle.net/10356/169607 10.3390/cancers14122866 35740532 2-s2.0-85131567213 12 14 2866 en MOE2014-T3-1-006 MOE-T2EP30120-0009 Cancers © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Super-Enhancers
Chromatin Looping
spellingShingle Science::Medicine
Super-Enhancers
Chromatin Looping
Tang, Seng Chuan
Vijayakumar, Udhaya
Zhang, Ying
Fullwood, Melissa Jane
Super-enhancers, phase-separated condensates, and 3D genome organization in cancer
description 3D chromatin organization plays an important role in transcription regulation and gene expression. The 3D genome is highly maintained by several architectural proteins, such as CTCF, Yin Yang 1, and cohesin complex. This structural organization brings regulatory DNA elements in close proximity to their target promoters. In this review, we discuss the 3D chromatin organization of super-enhancers and their relationship to phase-separated condensates. Super-enhancers are large clusters of DNA elements. They can physically contact with their target promoters by chromatin looping during transcription. Multiple transcription factors can bind to enhancer and promoter sequences and recruit a complex array of transcriptional co-activators and RNA polymerase II to effect transcriptional activation. Phase-separated condensates of transcription factors and transcriptional co-activators have been implicated in assembling the transcription machinery at particular enhancers. Cancer cells can hijack super-enhancers to drive oncogenic transcription to promote cell survival and proliferation. These dysregulated transcriptional programs can cause cancer cells to become highly dependent on transcriptional regulators, such as Mediator and BRD4. Moreover, the expression of oncogenes that are driven by super-enhancers is sensitive to transcriptional perturbation and often occurs in phase-separated condensates, supporting therapeutic rationales of targeting SE components, 3D genome organization, or dysregulated condensates in cancer.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Tang, Seng Chuan
Vijayakumar, Udhaya
Zhang, Ying
Fullwood, Melissa Jane
format Article
author Tang, Seng Chuan
Vijayakumar, Udhaya
Zhang, Ying
Fullwood, Melissa Jane
author_sort Tang, Seng Chuan
title Super-enhancers, phase-separated condensates, and 3D genome organization in cancer
title_short Super-enhancers, phase-separated condensates, and 3D genome organization in cancer
title_full Super-enhancers, phase-separated condensates, and 3D genome organization in cancer
title_fullStr Super-enhancers, phase-separated condensates, and 3D genome organization in cancer
title_full_unstemmed Super-enhancers, phase-separated condensates, and 3D genome organization in cancer
title_sort super-enhancers, phase-separated condensates, and 3d genome organization in cancer
publishDate 2023
url https://hdl.handle.net/10356/169607
_version_ 1773551411965984768