The Chromoscience

A Histone Variant Has Multiple Roles in Transcriptional Regulation

Benison P. Zerrudo
1–2 minutes

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https://www.nature.com/articles/s41467-021-22688-x

  • A promoter is a site on DNA to which the RNA polymerase can bind to initiate the transcription.[1]
  • Chromatin accessibility of a promoter is necessary for the regulation of transcriptional activity.
  • Histones are proteins that provide structural support to a chromosome.[2]
  • Long DNA molecules are wrap around complexes of histone proteins so that the DNA will fit into the cell nucleus.[2]
  • H2A.Z, a histone variant, has been shown to contribute to transcription regulation, however, its role is not well understood.
  • Researchers prepared maps of the position and accessibility of nucleosomes that contain the H2A.Z variant for all human RNA polymerase II promoters in epithelial, mesenchymal, and isogenic cancer cell lines.
  • The team is led by Lauren Cole of Florida State University in Tallahassee, Florida.
  • A nucleosome is a structural unit of a chromosome that contains a length of DNA coiled around a core of histones.[3]
  • The study revealed that many different types of active and inactive promoter structures are observed that differ in their nucleosome organization and sensitivity to MNase digestion.
  • MNase is an enzyme that digests DNA in regions that are not stably bound by proteins.[4]
  • Normally, DNA wrapped around the histones is protected from MNase digestion.[4]
  • Key aspects of an active chromatin structure include positioned H2A.Z MNase resistant nucleosomes before or after the transcription start site, and an MNase sensitive nucleosome at the transcription start site.
  • Additionally, the removal of H2A.Z leads to a significant increase in the accessibility of transcription factor binding sites.
  • Overall, the data suggest that the variant H2A.Z has numerous and distinct roles in gene expression regulation.

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Sources:

Cole, L., Kurscheid, S., Nekrasov, M. et al. Multiple roles of H2A.Z in regulating promoter chromatin architecture in human cells. Nat Commun 12, 2524 (2021). https://doi.org/10.1038/s41467-021-22688-x

[1] https://www.medicinenet.com/promoter/definition.htm

[2] https://www.genome.gov/genetics-glossary/histone

[3] Oxford Dictionary. https://languages.oup.com

[4] https://www.sciencedirect.com/topics/neuroscience/micrococcal-nuclease

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