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Mediator and cohesin connect gene expression and chromatin architecture

Author

Listed:
  • Michael H. Kagey

    (Whitehead Institute for Biomedical Research, 9 Cambridge Center)

  • Jamie J. Newman

    (Whitehead Institute for Biomedical Research, 9 Cambridge Center
    Massachusetts Institute of Technology)

  • Steve Bilodeau

    (Whitehead Institute for Biomedical Research, 9 Cambridge Center)

  • Ye Zhan

    (University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA)

  • David A. Orlando

    (Whitehead Institute for Biomedical Research, 9 Cambridge Center)

  • Nynke L. van Berkum

    (University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA)

  • Christopher C. Ebmeier

    (University of Colorado)

  • Jesse Goossens

    (University of Colorado)

  • Peter B. Rahl

    (Whitehead Institute for Biomedical Research, 9 Cambridge Center)

  • Stuart S. Levine

    (Massachusetts Institute of Technology)

  • Dylan J. Taatjes

    (University of Colorado)

  • Job Dekker

    (University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA)

  • Richard A. Young

    (Whitehead Institute for Biomedical Research, 9 Cambridge Center
    Massachusetts Institute of Technology)

Abstract

Transcription factors control cell-specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. Here we report that mediator and cohesin physically and functionally connect the enhancers and core promoters of active genes in murine embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with cohesin, which can form rings that connect two DNA segments. The cohesin-loading factor Nipbl is associated with mediator–cohesin complexes, providing a means to load cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by mediator and cohesin. Mediator and cohesin co-occupy different promoters in different cells, thus generating cell-type-specific DNA loops linked to the gene expression program of each cell.

Suggested Citation

  • Michael H. Kagey & Jamie J. Newman & Steve Bilodeau & Ye Zhan & David A. Orlando & Nynke L. van Berkum & Christopher C. Ebmeier & Jesse Goossens & Peter B. Rahl & Stuart S. Levine & Dylan J. Taatjes &, 2010. "Mediator and cohesin connect gene expression and chromatin architecture," Nature, Nature, vol. 467(7314), pages 430-435, September.
    • Handle: RePEc:nat:nature:v:467:y:2010:i:7314:d:10.1038_nature09380
    DOI: 10.1038/nature09380
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    Citations

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    Cited by:

    1. Ryuichiro Nakato & Toyonori Sakata & Jiankang Wang & Luis Augusto Eijy Nagai & Yuya Nagaoka & Gina Miku Oba & Masashige Bando & Katsuhiko Shirahige, 2023. "Context-dependent perturbations in chromatin folding and the transcriptome by cohesin and related factors," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Daniel Bsteh & Hagar F. Moussa & Georg Michlits & Ramesh Yelagandula & Jingkui Wang & Ulrich Elling & Oliver Bell, 2023. "Loss of cohesin regulator PDS5A reveals repressive role of Polycomb loops," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Alex Z. Kadhim & Ben Vanderkruk & Samantha Mar & Meixia Dan & Katarina Zosel & Eric E. Xu & Rachel J. Spencer & Shugo Sasaki & Xuanjin Cheng & Shannon L. J. Sproul & Thilo Speckmann & Cuilan Nian & Ro, 2024. "Transcriptional coactivator MED15 is required for beta cell maturation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Jiankang Wang & Masashige Bando & Katsuhiko Shirahige & Ryuichiro Nakato, 2022. "Large-scale multi-omics analysis suggests specific roles for intragenic cohesin in transcriptional regulation," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Sofía Muñoz & Andrew Jones & Céline Bouchoux & Tegan Gilmore & Harshil Patel & Frank Uhlmann, 2022. "Functional crosstalk between the cohesin loader and chromatin remodelers," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Alexandra D’Oto & Jie Fang & Hongjian Jin & Beisi Xu & Shivendra Singh & Anoushka Mullasseril & Victoria Jones & Ahmed Abu-Zaid & Xinyu Buttlar & Bailey Cooke & Dongli Hu & Jason Shohet & Andrew J. Mu, 2021. "KDM6B promotes activation of the oncogenic CDK4/6-pRB-E2F pathway by maintaining enhancer activity in MYCN-amplified neuroblastoma," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    7. Judith H. I. Haarhuis & Robin H. Weide & Vincent A. Blomen & Koen D. Flach & Hans Teunissen & Laureen Willems & Thijn R. Brummelkamp & Benjamin D. Rowland & Elzo Wit, 2022. "A Mediator-cohesin axis controls heterochromatin domain formation," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    8. Annkatrin Bressin & Olga Jasnovidova & Mirjam Arnold & Elisabeth Altendorfer & Filip Trajkovski & Thomas A. Kratz & Joanna E. Handzlik & Denes Hnisz & Andreas Mayer, 2023. "High-sensitive nascent transcript sequencing reveals BRD4-specific control of widespread enhancer and target gene transcription," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    9. Kadir Buyukcelebi & Xintong Chen & Fatih Abdula & Hoda Elkafas & Alexander James Duval & Harun Ozturk & Fidan Seker-Polat & Qiushi Jin & Ping Yin & Yue Feng & Serdar E. Bulun & Jian Jun Wei & Feng Yue, 2023. "Engineered MED12 mutations drive leiomyoma-like transcriptional and metabolic programs by altering the 3D genome compartmentalization," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    10. Sora Yoon & Aditi Chandra & Golnaz Vahedi, 2022. "Stripenn detects architectural stripes from chromatin conformation data using computer vision," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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