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Multiple roles of H2A.Z in regulating promoter chromatin architecture in human cells

Author

Listed:
  • Lauren Cole

    (Florida State University)

  • Sebastian Kurscheid

    (The Australian National University)

  • Maxim Nekrasov

    (The Australian National University)

  • Renae Domaschenz

    (The Australian National University)

  • Daniel L. Vera

    (Florida State University
    Department of Genetics, Blavatnik Institute, Paul F. Glenn Center for Biology of Aging Research, Harvard Medical School)

  • Jonathan H. Dennis

    (Florida State University)

  • David J. Tremethick

    (The Australian National University)

Abstract

Chromatin accessibility of a promoter is fundamental in regulating transcriptional activity. The histone variant H2A.Z has been shown to contribute to this regulation, but its role has remained poorly understood. Here, we prepare high-depth maps of the position and accessibility of H2A.Z-containing nucleosomes for all human Pol II promoters in epithelial, mesenchymal and isogenic cancer cell lines. We find that, in contrast to the prevailing model, many different types of active and inactive promoter structures are observed that differ in their nucleosome organization and sensitivity to MNase digestion. Key aspects of an active chromatin structure include positioned H2A.Z MNase resistant nucleosomes upstream or downstream of the TSS, and a MNase sensitive nucleosome at the TSS. Furthermore, the loss of H2A.Z leads to a dramatic increase in the accessibility of transcription factor binding sites. Collectively, these results suggest that H2A.Z has multiple and distinct roles in regulating gene expression dependent upon its location in a promoter.

Suggested Citation

  • Lauren Cole & Sebastian Kurscheid & Maxim Nekrasov & Renae Domaschenz & Daniel L. Vera & Jonathan H. Dennis & David J. Tremethick, 2021. "Multiple roles of H2A.Z in regulating promoter chromatin architecture in human cells," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22688-x
    DOI: 10.1038/s41467-021-22688-x
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    Cited by:

    1. László Imre & Péter Nánási & Ibtissem Benhamza & Kata Nóra Enyedi & Gábor Mocsár & Rosevalentine Bosire & Éva Hegedüs & Erfaneh Firouzi Niaki & Ágota Csóti & Zsuzsanna Darula & Éva Csősz & Szilárd Pól, 2024. "Epigenetic modulation via the C-terminal tail of H2A.Z," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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