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Dissecting super-enhancer hierarchy based on chromatin interactions

Author

Listed:
  • Jialiang Huang

    (Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health
    Harvard Medical School)

  • Kailong Li

    (University of Texas Southwestern Medical Center)

  • Wenqing Cai

    (Harvard Medical School)

  • Xin Liu

    (University of Texas Southwestern Medical Center)

  • Yuannyu Zhang

    (University of Texas Southwestern Medical Center)

  • Stuart H. Orkin

    (Harvard Medical School
    Howard Hughes Medical Institute)

  • Jian Xu

    (University of Texas Southwestern Medical Center)

  • Guo-Cheng Yuan

    (Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health)

Abstract

Recent studies have highlighted super-enhancers (SEs) as important regulatory elements for gene expression, but their intrinsic properties remain incompletely characterized. Through an integrative analysis of Hi-C and ChIP-seq data, here we find that a significant fraction of SEs are hierarchically organized, containing both hub and non-hub enhancers. Hub enhancers share similar histone marks with non-hub enhancers, but are distinctly associated with cohesin and CTCF binding sites and disease-associated genetic variants. Genetic ablation of hub enhancers results in profound defects in gene activation and local chromatin landscape. As such, hub enhancers are the major constituents responsible for SE functional and structural organization.

Suggested Citation

  • Jialiang Huang & Kailong Li & Wenqing Cai & Xin Liu & Yuannyu Zhang & Stuart H. Orkin & Jian Xu & Guo-Cheng Yuan, 2018. "Dissecting super-enhancer hierarchy based on chromatin interactions," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03279-9
    DOI: 10.1038/s41467-018-03279-9
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    Cited by:

    1. Sinan Xiong & Jianbiao Zhou & Tze King Tan & Tae-Hoon Chung & Tuan Zea Tan & Sabrina Hui-Min Toh & Nicole Xin Ning Tang & Yunlu Jia & Yi Xiang See & Melissa Jane Fullwood & Takaomi Sanda & Wee-Joo Chn, 2024. "Super enhancer acquisition drives expression of oncogenic PPP1R15B that regulates protein homeostasis in multiple myeloma," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Andrea Wilderman & Eva D’haene & Machteld Baetens & Tara N. Yankee & Emma Wentworth Winchester & Nicole Glidden & Ellen Roets & Jo Dorpe & Sandra Janssens & Danny E. Miller & Miranda Galey & Kari M. B, 2024. "A distant global control region is essential for normal expression of anterior HOXA genes during mouse and human craniofacial development," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    3. Yanli Liu & Zhong Wu & Jin Zhou & Dinesh K. A. Ramadurai & Katelyn L. Mortenson & Estrella Aguilera-Jimenez & Yifei Yan & Xiaojun Yang & Alison M. Taylor & Katherine E. Varley & Jason Gertz & Peter S., 2021. "A predominant enhancer co-amplified with the SOX2 oncogene is necessary and sufficient for its expression in squamous cancer," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    4. Claire Marchal & Nivedita Singh & Zachary Batz & Jayshree Advani & Catherine Jaeger & Ximena Corso-Díaz & Anand Swaroop, 2022. "High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Salah-Eddine Lamhamedi-Cherradi & Mayinuer Maitituoheti & Brian A. Menegaz & Sandhya Krishnan & Amelia M. Vetter & Pamela Camacho & Chia-Chin Wu & Hannah C. Beird & Robert W. Porter & Davis R. Ingram , 2022. "The androgen receptor is a therapeutic target in desmoplastic small round cell sarcoma," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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