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Sex-specific multi-level 3D genome dynamics in the mouse brain

Author

Listed:
  • Devin Rocks

    (Fordham University)

  • Mamta Shukla

    (University of Nebraska Medical Center)

  • Laila Ouldibbat

    (Fordham University)

  • Silvia C. Finnemann

    (Fordham University)

  • Achyuth Kalluchi

    (University of Nebraska Medical Center)

  • M. Jordan Rowley

    (University of Nebraska Medical Center)

  • Marija Kundakovic

    (Fordham University)

Abstract

The female mammalian brain exhibits sex hormone-driven plasticity during the reproductive period. Recent evidence implicates chromatin dynamics in gene regulation underlying this plasticity. However, whether ovarian hormones impact higher-order chromatin organization in post-mitotic neurons in vivo is unknown. Here, we mapped the 3D genome of ventral hippocampal neurons across the oestrous cycle and by sex in mice. In females, we find cycle-driven dynamism in 3D chromatin organization, including in oestrogen response elements-enriched X chromosome compartments, autosomal CTCF loops, and enhancer-promoter interactions. With rising oestrogen levels, the female 3D genome becomes more similar to the male 3D genome. Cyclical enhancer-promoter interactions are partially associated with gene expression and enriched for brain disorder-relevant genes and pathways. Our study reveals unique 3D genome dynamics in the female brain relevant to female-specific gene regulation, neuroplasticity, and disease risk.

Suggested Citation

  • Devin Rocks & Mamta Shukla & Laila Ouldibbat & Silvia C. Finnemann & Achyuth Kalluchi & M. Jordan Rowley & Marija Kundakovic, 2022. "Sex-specific multi-level 3D genome dynamics in the mouse brain," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30961-w
    DOI: 10.1038/s41467-022-30961-w
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