TY - JOUR
T1 - Sex-specific multi-level 3D genome dynamics in the mouse brain
AU - Rocks, Devin
AU - Shukla, Mamta
AU - Ouldibbat, Laila
AU - Finnemann, Silvia C.
AU - Kalluchi, Achyuth
AU - Rowley, M. Jordan
AU - Kundakovic, Marija
N1 - Funding Information:
This work was supported by the National Institutes of Health: the National Institute of Mental Health under Award Number R01MH123523 (to M.K.) and the National Institute of General Medical Sciences under Award Number R00GM127671 (to M.J.R.). S.C.F. holds the Kim B. and Stephen E. Bepler Professorship in Biology. We would like to thank: Yu Zhang for his assistance with nuclei sorting; Jidong Shan and Cristina Montagna for their assistance with FISH; Samuel Phillips for his assistance with massively parallel sequencing; and Tony Leesnitzer for his assistance with oestradiol quantification.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-30961-w
DO - 10.1038/s41467-022-30961-w
M3 - Article
C2 - 35705546
AN - SCOPUS:85132080164
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3438
ER -